Home » Posts tagged 'Antineoplastic'
Tag Archives: Antineoplastic
DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
.....FOR BLOG HOME CLICK HEREFlag and hits
ORGANIC SPECTROSCOPY
SUBSCRIBE
Subscribe in a reader
Enter your email address:
Delivered by FeedBurner
Subscribe to New Drug Approvals by Email
Recent Comments
 | shivkr2 on SPSR Excellence Award 2025 – S… |
 | Bonkasaurus on Infigratinib phosphate |
 | PALOVAROTENE | ORGAN… on Palovarotene |
| Pfizer just purchase… on Temanogrel | |
| Pfizer To Cash In On… on Temanogrel |
Mosperafenib
Mosperafenib
CAS 2649372-20-1
MF C20H17F2N5O4S MW 461.4 g/mol
- (3R)-N-{2-cyano-4-fluoro-3-[(3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)oxy]phenyl}-3-fluoropyrrolidine-1-sulfonamide
- (3R)-N-(2-cyano-4-fluoro-3-((3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)oxy)phenyl)-3-fluoropyrrolidine-1-sulfonamide
(3R)-N-{2-cyano-4-fluoro-3-[(3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)oxy]phenyl}-3-fluoropyrrolidine-1-sulfonamide
B-Raf (BRAF) inhibitor, antineoplastic, RG6344, RO7276389, RG 6344, RO 7276389, 881-730-4, B-Raf IN 2
Mosperafenib is a small molecule drug. The usage of the INN stem ‘-rafenib’ in the name indicates that Mosperafenib is a Raf (rapidly accelerated fibrosarcoma) kinase inhibitor. Mosperafenib has a monoisotopic molecular weight of 461.1 Da.
Mosperafenib (RG6344, RO7276389) is an investigational, oral, “paradox-breaker” BRAF inhibitor developed by Roche for treating BRAF-mutated cancers, particularly BRAF V600E-mutant metastatic colorectal cancer. It acts as a potent, selective inhibitor that avoids MAPK pathway overactivation in non-V600E contexts, showing superior preclinical activity and brain penetration compared to existing inhibitors like encorafenib.
Key Aspects of Mosperafenib:
- Mechanism: As a “paradox-breaker” BRAF inhibitor, it avoids the paradoxical MAPK pathway activation seen with earlier inhibitors. It inhibits BRAF mutants (
) and is effective in RAF dimer-mediated resistant models.
- Clinical Development: Currently in Phase I clinical trials for BRAF V600E-mutant colorectal cancer.
- Preclinical Performance: In studies, it demonstrated higher antitumor activity than encorafenib/cetuximab combinations, even in BRAFi-naïve models.
- Combination Potential: It is being evaluated in combination with cetuximab and FOLFOX.
- Targeting: It targets BRAF V600E/K/A/D mutations.
- OriginatorRoche
- ClassAntineoplastics; Fluorinated hydrocarbons; Fluorobenzenes; Nitriles; Phenyl ethers; Pyridones; Pyrrolidines
- Mechanism of ActionProto-oncogene protein b-raf inhibitors
- Phase IMalignant melanoma; Solid tumours
- 18 Sep 2025Chemical structure information added.
- 30 May 2025Efficacy, pharmacokinetics and adverse events data from a phase I trial in Solid tumors presented at the 61st Annual Meeting of the American Society of Clinical Oncology (ASCO-2025)
- 25 Apr 2025Efficacy, pharmacokinetics and adverse events data from a phase I trial in Solid tumors presented at the 116th Annual Meeting of the American Association for Cancer Research (AACR-2025)
SYN
SYN
3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide (Example 1)
R)-3-Fluoropyrrolidine-1-sulfonamide (1.26 g, 7.51 mmol, Eq: 2.1) and cesium carbonate (2.56 g, 7.87 mmol, Eq: 2.2) were suspended in dry DMF (10.2 ml) under an argon atmosphere. The reaction was stirred at 50° C. for 30 min. The reaction mixture was cooled to rt and a solution of 3,6-difluoro-2-((3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)oxy)benzonitrile (1.12 g, 3.58 mmol, Eq: 1.0) in DMF (25.5 ml) was added. The reaction mixture was stirred at 100° C. for 15 h, then concentrated in vacuo. The residue was taken up in sat. aq. NH 4Cl (100 mL) and EtOAc (100 mL). The phases were separated, and the aqueous layer was extracted further with 2×100 mL EtOAc. The combined organic layers were washed with water (200 mL) and brine (200 mL), dried (Na 2SO 4), filtered and concentrated in vacuo. The water layer was back-extracted with EtOAc (3×100 mL). The combined organic extracts were washed with brine (200 mL), dried (Na 2SO 4), filtered and concentrated in vacuo. The residue was diluted with DCM and MeOH, and concentrated onto silica. Purification by flash chromatography (120 g, 0.5-2% MeOH/DCM) gave an off-white solid which was triturated with 1:1 heptane/DCM (20 mL) with sonication, then dried in vacuo to give the title compound as a colourless solid (1.087 g, 66% yield). MS (ESI) m/z: 426.2 [M+H] +. Chiral SFC: RT=4.594 min [Chiralpak IC column, 4.6×250 mm, 5 μm particle size (Daicel); gradient of 20-40% MeOH containing 0.2% NHEt 2 over 8 min; flow: 2.5 mL/min; 140 bar backpressure].
SYN
Refences compounds AR-25, AR-30 and AR-31 were prepared according to the synthesis disclosed in WO2012/118492 in example 25, example 30 and example 31 respectively.
6-hydroxy-3-methyl-quinazolin-4-one
2-Amino-5-hydroxybenzoic acid (10 g, 65.3 mmol, Eq: 1.0) and A-methylformamide (30 g, 29.9 mL, 503 mmol, Eq: 7.7) were heated at 145 °C for 21 h 45 min, then cooled to rt. The reaction mixture was diluted with 50 mL H2O and stirred at rt for 20 min. The resulting precipitate was collected by filtration. The light brown solid was washed 3 × with 20 mL water. The solid was taken up in toluene and evaporated to dryness (3 ×). The solid was dried in vacuo at 40 °C overnight under high vacuum to give the title compound as a light brown solid (10.3 g, 89% yield). MS (ESI) mlz: 177.1 [M+H]+.
3.6-difluoro-2-(3-methyl-4-oxo-quinazolin-6-yl)oxy-benzonitrile
Cesium carbonate (3.22 g, 9.79 mmol, Eq: 1.15) was added at rt to a solution of 6-hydroxy-3-methylquinazolin-4-one (1500 mg, 8.51 mmol, Eq: 1.0) in N,N-dimethylformamide (35 mL). The mixture was stirred for 30 min at rt then 2,3,6-trifluorobenzonitrile (1.47 g, 1.08 ml, 9.37 mmol, Eq: 1.1) was added. After 1 h, the reaction was cooled on ice and diluted with water (120 mL). The resultant solid was collected by filtration, washed with iced water (100 mL) and heptane (100 mL) and suction-dried. The solid was taken up in toluene and evaporated to dryness (3 ×) then dried overnight in vacuo to give the title compound as a light brown solid (2.58 g, 97% yield). MS (ESI) m/z: 314.1 [M+H]+.
(3R)-3 -fluoropyrrolidine- 1 -sulfonamide
(R)-3 -Fluoropyrrolidine hydrochloride (1.8 g, 14.3 mmol, Eq: 1.2) was added to a solution of sulfuric diamide (1.148 g, 11.9 mmol, Eq: 1.0) and triethylamine (2.42 g, 3.33 mL, 23.9 mmol, Eq: 2) in dioxane (10 mL). The reaction was stirred in a sealed tube at 115 °C for 15.5 h then cooled to rt and concentrated in vacuo. The residue was diluted with DCM, evaporated with silica gel to dryness and transferred to a column. Purification by flash chromatography (40 g silica, 80% EtOAc) gave the title compound as a white crystalline solid (1.82 g, 91% yield). MS (ESI) m/z: 169.1 [M+H]+.
(3S)-3 -fluoropyrrolidine- 1 -sulfonamide
Triethylamine (304 mg, 419 μl, 3.01 mmol, Eq: 2.0) was added to a suspension of sulfuric diamide (146 mg, 1.5 mmol, Eq: 1.0) and (S)-3 -fluoropyrrolidine hydrochloride (234 mg, 1.8 mmol, Eq: 1.2) in dioxane (1.3 ml). The reaction was stirred in a sealed tube at 115°C for 16 h 35 min, then concentrated in vacuo. The residue was diluted with MeOH and evaporated with silica gel to dryness and transferred to a column. Purification by flash chromatography (40 g silica, 0-8% MeOH/DCM) gave the title compound as a light yellow solid (193 mg, 75% yield). MS (ESI) m/z: 169.1 [M+H]+.
(3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1 -sulfonamide (Example 1)
(R)-3-Fluoropyrrolidine-1-sulfonamide (1.26 g, 7.51 mmol, Eq: 2.1) and cesium carbonate (2.56 g, 7.87 mmol, Eq: 2.2) were suspended in dry DMF (10.2 ml) under an argon atmosphere. The reaction was stirred at 50 °C for 30 min. The reaction mixture was cooled to rt and a solution of 3,6-difluoro-2-((3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)oxy)benzonitrile (1.12 g, 3.58 mmol, Eq: 1.0) in DMF (25.5 ml) was added. The reaction mixture was stirred at 100 °C for 15 h, then concentrated in vacuo. The residue was taken up in sat. aq. NH4Cl (100 mL) and EtOAc (100 mL). The phases were separated, and the aqueous layer was extracted further with 2 x 100 mL EtOAc. The combined organic layers were washed with water (200 mL) and brine (200 mL), dried (Na2SO4), filtered and concentrated in vacuo. The water layer was back-extracted with EtOAc (3 x 100 mL). The combined organic extracts were washed with brine (200 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was diluted with DCM and MeOH, and concentrated onto silica. Purification by flash chromatography (120 g, 0.5-2% MeOH/DCM) gave an off-white solid which was triturated with 1 : 1 heptane/DCM (20 mL) with sonication, then dried in vacuo to give the title compound as a colourless solid (1.087 g, 66% yield). MS (ESI) mlz: 426.2 [M+H]+. Chiral SFC: RT = 4.594 min [Chiralpak IC column, 4.6 x 250 mm, 5μm particle size (Daicel); gradient of 20 – 40% MeOH containing 0.2% NHEt2 over 8 min; flow: 2.5 mL/min; 140 bar backpressure],
(3S)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1 -sulfonamide (Example 2)
(S)-3-Fluoropyrrolidine-1-sulfonamide (181 mg, 1.08 mmol, Eq: 2.1) was dissolved in DMF (1.6 ml). At rt cesium carbonate (368 mg, 1.13 mmol, Eq: 2.2) was added and the reaction mixture was stirred at 50 °C for 30 min. The reaction mixture was cooled to rt and a solution of 3,6-difluoro-2-((3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)oxy)benzonitrile (160.8 mg, 513 μmol, Eq: 1.0) in DMF (4 ml) was added. The reaction mixture was stirred at 105 °C for 2 h 50 min then concentrated in vacuo. The residue was taken up in DCM and washed with sat. aq. NH4Cl. The aq. layer was back-extracted twice with DCM. The combined organic layers were dried over Na2SO4, filtrated and evaporated. The residue (brown oil) was diluted with DCM and transferred to a column. Purification by flash chromatography (80 g, 0-100% EtOAc in DCM) gave a solid which was further purified by SFC to give the title compound as a light yellow solid (119 mg, 50% yield). MS (ESI) m/z: 426.2 [M+H]+. Chiral SFC: RT = 4.411 min [Chiralpak IC column, 4.6 x 250 mm, 5μm particle size (Daicel); gradient of 20 – 40% MeOH containing 0.2% NHEt2 over 8 min; flow: 2.5 mL/min; 140 bar backpressure].
PAT
New methylquinazolinone derivatives
Publication Number: AU-2020403443-A1
Priority Date: 2019-12-10
- Methylquinazolinone derivativesPublication Number: US-2024174621-A1Priority Date: 2019-12-10
- New methylquinazolinone derivativesPublication Number: EP-4073065-B1Priority Date: 2019-12-10Grant Date: 2025-02-19
- Methylquinazolinone derivativesPublication Number: US-2022298119-A1Priority Date: 2019-12-10
- Novel BRAF inhibitors as anomalous breakersPublication Number: CN-114746405-BPriority Date: 2019-12-10Grant Date: 2024-03-26
- New BRAF inhibitors as paradox breakersPublication Number: AU-2020403082-A1Priority Date: 2019-12-10
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
////////////////mosperafenib, B-Raf (BRAF) inhibitor, antineoplastic, RG6344, RO7276389, RG 6344, RO 7276389, 881-730-4, B-Raf IN 2
Mocaciclib
Mocaciclib
CAS 2766124-39-2
MF C33H36FN9O2 MW609.71
- 2-fluoro-N-[1-[2-[[[2-[[(3R,4R)-3-hydroxypiperidin-4-yl]methylamino]-8-propan-2-ylpyrazolo[1,5-a][1,3,5]triazin-4-yl]amino]methyl]phenyl]isoquinolin-6-yl]prop-2-enamide
- 2-Fluoro-N-[1-[2-[[[2-[[[(3R,4R)-3-hydroxy-4-piperidinyl]methyl]amino]-8-(1-methylethyl)pyrazolo[1,5-a]-1,3,5-triazin-4-yl]amino]methyl]phenyl]-6-isoquinolinyl]-2-propenamide
- 2-fluoro-N-[1-[2-[[[2-[[(3R,4R)-3-hydroxypiperidin-4-yl]methylamino]-8-propan-2-ylpyrazolo[1,5-a][1,3,5]triazin-4-yl]amino]methyl]phenyl]isoquinolin-6-yl]prop-2-enamide
cyclin-dependent kinase (CDK) inhibitor, antineoplastic, Q 901, CDK7-IN-21,
- OriginatorThe Lead Discovery Center; The Max Planck Institute of Biochemistry
- DeveloperQurient Co
- ClassAntineoplastics; Small molecules
- Mechanism of ActionCyclin-dependent kinase-activating kinase inhibitors
- Phase I/IISolid tumours
- 31 May 2024Preliminary efficacy, pharmacodynamics, pharmacokinetics and adverse events data from a phase I/II trial in Solid tumours presented at the 60th Annual Meeting of the American Society of Clinical Oncology (ASCO-2024)
- 21 May 2024Qurient Therapeutics enters into an Cooperative Research and Development Agreement (CRADA) with the US National Cancer Institute (NCI) for phase I/II trial in Small cell lung cancer (SCLC) and Solid tumours
- 21 May 2024Qurient Therapeutics plans phase I/II trial in Small cell lung cancer (SCLC) and Solid tumours
Mocaciclib (Q-901) is an orally bioavailable, selective cyclin-dependent kinase (CDK) inhibitor with potent activity against CDK2, CDK4, and CDK6. Preclinical data show that Mocaciclib inhibits CDK2/cyclin E with an IC₅₀ of 1.1 nM, CDK4/cyclin D1 with an IC₅₀ of 2.5 nM, and CDK6/cyclin D3 with an IC₅₀ of 4.1 nM, demonstrating high potency in enzymatic assays. In cancer cell lines, Mocaciclib suppresses retinoblastoma protein (Rb) phosphorylation, leading to G1 cell cycle arrest and growth inhibition in Rb-positive tumor models. It has shown antiproliferative effects in various preclinical models, including breast and lung cancers.
Mocaciclib is a selective inhibitor of cyclin-dependent kinase 7 (CDK7), with potential antineoplastic activity. Upon administration, mocaciclib selectively targets, covalently binds to and inhibits the activity of CDK7, thereby inhibiting CDK7-mediated signaling. The inhibition of CDK7 prevents phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II, thereby preventing transcription of important cancer-promoting genes. It prevents phosphorylation of the cell cycle kinases CDK1, 2, 4, and 6, thereby disrupting uncontrolled cell cycle progression. Altogether, this may induce apoptosis, cause cell cycle arrest, inhibit DNA damage repair and inhibit tumor cell proliferation in certain cancers that are dependent on CDK7-mediated transcriptional regulation and signaling. CDK7, a serine/threonine kinase, plays a role in controlling cell cycle progression and transcriptional regulation, and promotes the expression of key oncogenes through the phosphorylation of RNA polymerase II. It is overexpressed in multiple cancers.
SYN
SYN
This is compound 64, as disclosed in WO2O19/197546.
PAT
- Compounds having cyclin-dependent kinase(cdk)-inhibitory functionPublication Number: WO-2022117504-A1Priority Date: 2020-12-02
- Substituted pyrazolo[1,5-a]pyrimidines and pyrazolo[1,5-a][1,3,5]triazines as CDK inhibitorsPublication Number: US-11858937-B2Priority Date: 2018-04-11Grant Date: 2024-01-02
- Pharmaceutically active pyrazolo-triazine and/or pyrazolo-pyrimidine derivativesPublication Number: US-2021139483-A1Priority Date: 2018-04-11
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
//////////mocaciclib, cyclin-dependent kinase (CDK) inhibitor, antineoplastic, Q 901, CDK7-IN-21,
Mobinitinib
Mobinitinib
CAS1402709-93-6
MF C22H23Cl2N7 MW456.37
6-chloro-7-{4-[(4-chlorophenyl)methyl]piperazin-1-yl}-2-(1,3-dimethyl-1Hpyrazol-4-yl)-3H-imidazo[4,5-b]pyridine
6-chloro-7-{4-[(4-chlorophenyl)methyl]piperazin-1-yl}-2-(1,3-dimethyl-1Hpyrazol-4-yl)-3H-imidazo[4,5-b]pyridine
dual FMS-like tyrosine kinase-3 (FLT3)-Aurora kinase inhibitor, antineoplastic, CCT241736, CCT 241736, ZE94SP78UG, EP0042, EP 0042
Mobinitinib (CCT241736) is an investigational, orally bioavailable, small-molecule, dual inhibitor targeting Aurora kinase and FLT3 (including ITD and D835Y mutations). It shows potent antineoplastic activity in preclinical models, including acute myeloid leukemia (AML), by inhibiting tumor cell proliferation and disrupting mitotic spindle assembly. It is a distinct compound from similarly named drugs like Momelotinib or Binimetinib.
Key Details About Mobinitinib (CCT241736)
- Mechanism of Action: Acts as a dual inhibitor of Aurora kinases (A and B) and FMS-related tyrosine kinase 3 (FLT3). By inhibiting these kinases, it interferes with mitotic spindle assembly and chromosome segregation, leading to cell cycle arrest.
- Target Indications: Primarily studied for its potential to treat hematological malignancies and solid tumors that overexpress FLT3 or Aurora kinases. Preclinical studies show effectiveness in FLT3-ITD positive AML cell lines (e.g., MOLM-13, MV4-11).
- Preclinical Activity: Demonstrates strong anti-proliferative activity with
values in the sub-micromolar range (e.g., 0.1–0.3
M) in certain human tumor cell lines. It has shown significant tumor growth inhibition in mouse xenograft models at doses of 50-100 mg/kg.
- Chemical Properties: It is a 1H-imidazo[5-b]pyridine derivative.
It is important to distinguish mobinitinib (CCT241736) from momelotinib, a JAK1/JAK2 inhibitor approved for myelofibrosis, and binimetinib, a MEK inhibitor for melanoma.
Mobinitinib is an orally bioavailable inhibitor of both the serine/threonine protein kinase Aurora kinase and FMS-related tyrosine kinase 3 (FLT3; STK1; CD135; FLK2), with potential antineoplastic activity. Upon oral administration, mobinitinib specifically binds to and inhibits Aurora kinase and FLT3, which interferes with the activation of Aurora kinase- and FLT3-mediated signal transduction pathways. This may result in the disruption of the assembly of the mitotic spindle apparatus, the disruption of chromosome segregation and the inhibition of cell proliferation in tumor cells that overexpress Aurora kinase and/or FLT3. Aurora kinase plays essential roles in mitotic checkpoint control during mitosis. Aurora kinase and FLT3 are overexpressed in a variety of cancers and play key roles in tumor cell proliferation.
MOBINITINIB is a small molecule drug with a maximum clinical trial phase of II and has 1 investigational indication.
Study to Evaluate the Safety and Tolerability of EP0042
CTID: NCT04581512
Phase: Phase 1/Phase 2
Status: Recruiting
Date: 2025-10-14
SYN
5-Chloro-4-(4-(4-chlorobenzyl)piperazin-1-yl)-3-nitropyridin-2-amine
[00119] To a mixture of 2-amino-4,5-dichloro-3-nitropyridine (0.152 g, 0.73 mmol) and isopropanol (22 mL) was added 1 -(4-chlorobenzyl)piperazine (0.165 g, 0.78 mmol) followed by diisopropylethylamine (0.17 mL, 0.97 mmol). The reaction mixture was heated at 45 °C for 18 h, then allowed to cool to room temperature, and diluted with isopropanol (5 mL). The precipitate was collected by filtration, washed with isopropanol and diethyl ether. The title compound was thus obtained as a yellow solid (0.215 g, 77%); 1H-NMR (500 MHz, DMSO-d6) 2.48 (br s, obscured by DMSO peak, 4H, piperazine C-H), 3.06 (br t, J = 4.3 Hz, 4H, piperazine C-H), 3.52 (s, 2H, NCH2C6H4Cl), 6.95 (s, 2H, NH2), 7.35 (d, J = 8.5 Hz, 2H) and 7.38 (d, J = 8.5 Hz, 2H) (3,5-ArH and 2,6- ArH), 8.06 (s, 1 H, 6-H); LC – MS (ESI, m/z): Rt = 1 .70 min – 382, 384, 386 [(M+H)+, Cl2 isotopic pattern].
6-Chloro-7-(4-(4-chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine
[00120] To a mixture of 5-chloro-4-(4-(4-chlorobenzyl)piperazin-1 -yl)-3-nitropyridin-2-amine (0.076 g, 0.20 mmol) and EtOH (4.0 ml.) was added 1 ,3-dimethyl-1 H-pyrazole-4-carbaldehyde (0.027 g, 0.22 mmol) followed by a freshly prepared aqueous solution of Na2S2O4 (1 M; 0.85 mL, 0.85 mmol). The reaction mixture was stirred at 80 °C for 24 h, it was then allowed to cool to room temperature, concentrated in vacuo, and the residue was absorbed on silica gel and placed on a 10 g isolute silica column. Elution with ethyl acetate / dichloromethane (v/v; 1 :1 ), and then 4% methanol in ethyl acetate / dichloromethane (v/v; 1 :1 ) afforded the title compound as a white solid after trituration with diethyl ether (0.023 g, 25%).
[00121 ] 1 H-NMR (500 MHz, DMSO-d6) 2.51 (s, obscured by solvent peak, pyrazole 3-CH3), 2.57 (br s, 4H, piperazine C-H), 3.54 (s, 2H, N-CH2C6H4Cl), 3.68 (br s, 4H, piperazine C-H), 3.84 (s, 3H, pyrazole N-Me), 7.37 (d, J = 8.5 Hz, 2H) and 7.40 (d, J = 8.5 Hz, 2H) (C6H4Cl), 8.02 (s, 1 H), and 8.18 (s, 1 H) (pyrazole 5-H, and imidazo[4,5-b]pyridine 5-H), 12.95 (br s, 1 H, imidazo[4,5-b]pyridine N-H); LC – MS (ESI, m/z): Rt = 1.97 min – 456, 458, 460 [(M+H)+, Cl2 isotopic pattern].
[00122] HRMS: Found: 456.1457, calculated for C22H24Cl2N7 (M+H)+: 456.1465.
LIT
- FLT3 Inhibitors in Acute Myeloid Leukemia: Challenges and Recent Developments in Overcoming ResistancePublication Name: Journal of Medicinal ChemistryPublication Date: 2021-03-10PMID: 33719439DOI: 10.1021/acs.jmedchem.0c01851
- Quizartinib-resistant FLT3-ITD acute myeloid leukemia cells are sensitive to the FLT3-Aurora kinase inhibitor CCT241736Publication Name: Blood AdvancesPublication Date: 2020-04-13PMCID: PMC7160287PMID: 32282883DOI: 10.1182/bloodadvances.2019000986
- Metabolism of the dual FLT-3/Aurora kinase inhibitor CCT241736 in preclinical and human in vitro models: Implication for the choice of toxicology speciesPublication Name: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical SciencesPublication Date: 2019-11-01PMCID: PMC6892276PMID: 30953752DOI: 10.1016/j.ejps.2019.04.004
- Optimization of Imidazo[4,5-b]pyridine-Based Kinase Inhibitors: Identification of a Dual FLT3/Aurora Kinase Inhibitor as an Orally Bioavailable Preclinical Development Candidate for the Treatment of Acute Myeloid LeukemiaPublication Name: Journal of Medicinal ChemistryPublication Date: 2012-10-08PMCID: PMC3483018PMID: 23043539DOI: 10.1021/jm300952s
PAT
- Pharmaceutically active compoundsPublication Number: WO-2013190319-A1Priority Date: 2012-06-21
- Compound and, pharmaceutical compositionPublication Number: BR-112014032142-B1Priority Date: 2012-06-21
- Pharmaceutically active compoundsPublication Number: US-9447092-B2Priority Date: 2012-06-21Grant Date: 2016-09-20
- Pharmaceutically active compoundsPublication Number: CA-2876357-A1Priority Date: 2012-06-21
- Pharmaceutically active compoundsPublication Number: US-2015266868-A1Priority Date: 2012-06-21
- PHARMACEUTALLY ACTIVE COMPOUNDSPublication Number: RU-2015101702-APriority Date: 2012-06-21
- Pharmaceutically active compoundsPublication Number: SI-2864328-T1Priority Date: 2012-06-21
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
////////////////mobinitinib, antineoplastic, CCT241736, CCT 241736, ZE94SP78UG, EP0042, EP 0042
Mevrometostat
Mevrometostat
CAS 1844849-10-0
MF C22H24Cl2N2O5 MW467.3 g/mol
5,8-dichloro-2-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-7-[(R)-methoxy(oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1-one
5,8-dichloro-7-[(R)-methoxy(oxetan-3-yl)methyl]-2-[(4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3,4-
dihydroisoquinolin-1(2H)-one
enhancer of zeste homolog 2 (EZH2) inhibitor, antineoplastic, PF-06821497, PF 06821497, S4L4MM20B6
Mevrometostat (development code PF-06821497) is an investigational anticancer drug that functions as a potent and selective inhibitor of enhancer of zeste homolog 2 (EZH2).[1][2] Currently under development by Pfizer, mevrometostat is being investigated primarily for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in combination with enzalutamide.
PF-06821497 is under investigation in clinical trial NCT03460977 (PF-06821497 Treatment Of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma).
Mevrometostat is an orally available selective inhibitor of the histone lysine methyltransferase (HMT) enhancer of zeste homolog 2 (EZH2), with potential antineoplastic activity. Upon oral administration, mevrometostat selectively targets, binds to and inhibits the activity of EZH2. Inhibition of EZH2 specifically prevents the methylation of histone H3 on lysine 27 (H3K27). This decrease in histone methylation alters gene expression patterns associated with cancer pathways and results in decreased proliferation of EZH2-expressing cancer cells. EZH2, an HMT class enzyme and the catalytic subunit of the polycomb repressive complex 2 (PRC2), is overexpressed or mutated in a variety of cancer cells and plays a key role in tumor cell proliferation; its expression is correlated with tumor initiation, progression, stem cell self-renewal, migration and angiogenesis.
MEVROMETOSTAT is a small molecule drug with a maximum clinical trial phase of II and has 1 investigational indication.
Synthesis
LAST STEP CONDITIONS
METHYL IODIDE REAGENT, Tetrahydrofuran , Potassium tert-butoxide
NEXT Hydrogen, Platinum dioxide,
SYN
Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497)Publication Name: Journal of Medicinal ChemistryPublication Date: 2017-12-27PMID: 29211475DOI: 10.1021/acs.jmedchem.7b01375
5,8-dichloro-2-[(4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-[(R)-
methoxy(oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one (23a) and 5,8-dichloro-2-[(4-
methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-[(S)-methoxy(oxetan-3-yl)methyl]-
3,4-dihydroisoquinolin-1(2H)-one (23b)
Multiple batches of (±)-5,8-dichloro-2-[(4-methoxy-6-
methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-[methoxy-
(oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one 40
were combined (140 mg total), and the enantiomers separated
by preparative chiral SFC [Column: (R,R)Whelk O1
250mm*30mm,5µ; mobile phase: EtOH; wavelength: 220
nm] to give, after lyophilization, 23a (50.3 mg, 36%) as a
white solid, and 23b (22.8 mg, 16%) as a white solid. A
small-molecule X-Ray crystal structure of 23a showed it to
have absolute (R) stereochemistry. A small-molecule X-Ray crystal structure of 23b confirmed
the expected absolute (S) stereochemistry.
5,8-dichloro-2-[(4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-[(R)-
methoxy(oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one (23a). After chiral SFC and
lyophilization, 23a (50.3 mg, 36%) was obtained as a white solid. LCMS m/z 489 [M+Na]+; 1H
NMR (400 MHz, CDCl3) δ 12.34 (br s, 1H), 7.49 (s, 1H), 5.93 (s, 1H), 5.05 (d, J=6.0 Hz, 1H),
4.78-4.61 (m, 6H), 3.88 (s, 3H), 3.50-3.48 (m, 2H), 3.38-3.37 (m, 1H), 3.31 (s, 3H), 2.94 (t,
J=6.2 Hz, 2H), 2.35 (s, 3H). [α]D
22 +67.7° (c 0.1, MeOH); Chiral analysis: 100% ee; retention
time 9.85 min; column (R,R)Whelk O1, 250×4.6mm I.D., 5µ; mobile phase 50% ethanol (0.05%
DEA) in CO2; wavelength 220 nm. A crystalline sample of 23a was obtained by dissolving the
lyophilized powder in hot isopropanol in a 1 dram vial, then letting the vial stand in a capped
TLC chamber containing a layer of hexanes in the bottom, which allowed slow diffusion of hexanes into isopropanol. After two days, crystals (square plates) were collected. A smallmolecule X-Ray crystal structure of 23a showed it to have absolute (R) stereochemistry.
Crystallographic data are available in the Supporting Information.
syn
Pfizer Inc.
United States, US20150361067
REF
- Computational exploration in search for novel natural product-derived EZH2 inhibitors for advancing anti-cancer therapyPublication Name: Molecular DiversityPublication Date: 2025-02-19PMID: 39969739DOI: 10.1007/s11030-025-11128-3
- TTD: Therapeutic Target Database describing target druggability informationPublication Name: Nucleic Acids ResearchPublication Date: 2023-09-15PMCID: PMC10767903PMID: 37713619DOI: 10.1093/nar/gkad751
- BLM overexpression as a predictive biomarker for CHK1 inhibitor response in PARP inhibitor–resistant BRCA -mutant ovarian cancerPublication Name: Science Translational MedicinePublication Date: 2023-06-21PMCID: PMC10758289PMID: 37343085DOI: 10.1126/scitranslmed.add7872
- Structural modification aimed for improving solubility of lead compounds in early phase drug discoveryPublication Name: Bioorganic & Medicinal ChemistryPublication Date: 2022-02-15PMID: 35033884DOI: 10.1016/j.bmc.2022.116614
- High-Throughput Screening to Identify Inhibitors of the Type I Interferon–Major Histocompatibility Complex Class I Pathway in Skeletal MusclePublication Name: ACS Chemical BiologyPublication Date: 2020-05-27PMCID: PMC7859889PMID: 32459468DOI: 10.1021/acschembio.0c00343
- Translational Pharmacokinetic-Pharmacodynamic Modeling for an Orally Available Novel Inhibitor of Epigenetic Regulator Enhancer of Zeste Homolog 2Publication Name: The Journal of Pharmacology and Experimental TherapeuticsPublication Date: 2020-05PMID: 32094296DOI: 10.1124/jpet.119.263491
- Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497)Publication Name: Journal of Medicinal ChemistryPublication Date: 2017-12-27PMID: 29211475DOI: 10.1021/acs.jmedchem.7b01375
- Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylationPublication Name: BloodPublication Date: 2011-02-24PMCID: PMC3062411PMID: 21190999DOI: 10.1182/blood-2010-11-321208
PAT
- Novel 3-amino-3,4,6-trideoxyglycals, their production methods and anthracyclines obtained from these glycalsPublication Number: JP-S6110572-APriority Date: 1984-06-15
- CARBON HYDROGENATION METHOD WITH INCREASED RETENTION OF SOLIDS IN FLUID BED REACTORSPublication Number: DE-3245494-A1Priority Date: 1981-12-21
- Group extraction of organic compounds present in liquid samplesPublication Number: US-3966410-APriority Date: 1972-07-24Grant Date: 1976-06-29
- PRMT5 inhibitors and uses thereofPublication Number: US-12448388-B2Grant Date: 2025-10-21
- KRAS G12D modulating compoundsPublication Number: US-12448400-B2Grant Date: 2025-10-21
- Fungicidal, acaricidal and insecticidal composition comprising imidazole derivatives as active ingredient and process for producing the active ingredientsPublication Number: HU-206245-BPriority Date: 1987-03-13
- Fluorine derivatives of vitamin d _and process for producing the samePublication Number: CA-1297869-CPriority Date: 1986-10-20Grant Date: 1992-03-24
- Fluorine derivatives of vitamin d3 and process for producing the samePublication Number: EP-0264880-B1Priority Date: 1986-10-20Grant Date: 1991-03-13
- Fluorine derivatives of vitamin D3 and process for producing the samePublication Number: EP-0264880-A1Priority Date: 1986-10-20
- Process for production of new derivatives of imidasolil-alkyl-guanidin and medical preparatives containing these substancesPublication Number: HU-198024-BPriority Date: 1985-04-02
WO-0003990-A1 WO-0059513-A1 WO-0127114-A1 WO-02100354-A2 WO-2004029040-A1 WO-2004033420-A1 WO-2004078712-A2 WO-2004092118-A2 WO-2005000869-A1 WO-2005040109-A1 WO-2005082368-A1 WO-2006083424-A2 WO-2007022638-A1 WO-2007030089-A1 WO-2007058503-A1 WO-2008116833-A1 WO-2009005690-A2 WO-2009142969-A1 WO-2010015656-A2 WO-2010123599-A9 WO-2011102800-A1 WO-2011115818-A1 WO-2011139702-A2 WO-2012033149-A1 WO-2012037372-A2 WO-2012069856-A1 WO-2012097013-A1 WO-2012112969-A1 WO-2012129673-A1 WO-2012130912-A1 WO-2013096679-A1 WO-2013096680-A1 WO-2013102242-A1 WO-2013142525-A1 WO-2013177983-A1 WO-2014037498-A2 WO-2014057415-A2 WO-2015193765-A1 WO-2020190754-A1 WO-2021163064-A9 WO-2022053990-A1 WO-2022058405-A2 WO-2022087149-A2 WO-2022087230-A1 WO-2022164789-A1 WO-2022164789-A9 WO-2022212746-A1 WO-2022212748-A1 WO-2022221304-A1 WO-2022232435-A1 WO-2022261243-A1 WO-2022271650-A1 WO-2022271659-A1 WO-2022271677-A1 WO-2022271684-A1 WO-2023015164-A1 WO-2023041674-A1 WO-2023055885-A2 WO-2023061446-A1 WO-2023076554-A9 WO-2023076983-A1 WO-2023077030-A1 WO-2023100131-A1 WO-2023108563-A1 WO-2023111810-A1 WO-2023114460-A1 WO-2023122581-A2 WO-2023122615-A1 WO-2023147418-A1 WO-2023166418-A2 WO-2023166420-A1 WO-2023178181-A1 WO-2023178354-A1 WO-2023183817-A1 WO-2023196784-A1 WO-2023205719-A1 WO-2023205850-A1 WO-2023212504-A1 WO-2023218320-A1 WO-2023242769-A1 WO-2023249714-A1 WO-2024003773-A1 WO-2024006929-A1 WO-2024009191-A1 WO-2024015566-A1 WO-2024019995-A1 WO-2024020534-A2 WO-2024033513-A1 WO-2024035688-A1 WO-2024064668-A1 WO-2024074977-A1 WO-2024086094-A1 WO-2024105563-A1 WO-2024187153-A1 WO-2024189607-A1 WO-2024192373-A1 WO-2024193570-A1 WO-2024193570-A9 WO-2024209339-A1 WO-2024213979-A1 WO-2024215754-A1 WO-2024218686-A1 WO-2024220917-A1 WO-2024246965-A1 WO-2025006704-A1 WO-2025006720-A1 WO-2025024663-A1 WO-2025024811-A1 WO-2025031307-A1 WO-2025038726-A2 WO-2025049966-A2 WO-2025049966-A9 WO-2025054347-A1 WO-2025054530-A1 WO-2025059027-A1 WO-2025085536-A1 WO-2025094035-A1 WO-2025096589-A1 WO-2025121805-A1 WO-2025121807-A1 WO-2025137640-A1 WO-2025151706-A1 WO-2025245003-A1 WO-9012007-A1 WO-9522521-A1 WO-9954305-A1
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
Mechanism of action
Mevrometostat is a small molecule inhibitor that targets EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2).[1][3] EZH2 plays a crucial role in epigenetic regulation by modifying gene expression patterns that control cellular fate decisions, including differentiation and self-renewal.[1]
In prostate cancer, EZH2 dysregulation contributes to treatment resistance through multiple pathways, including:
- Silencing of tumor suppressor genes
- Activation of androgen receptor transcription factors
- Promotion of neuroendocrine transdifferentiation[4]
Mevrometostat demonstrates dose-dependent EZH2 inhibition, leading to reactivation of tumor suppressor genes while suppressing genes involved in tumor progression.[5]
Clinical development
Phase I/II trials
The primary clinical evaluation of mevrometostat is being conducted through a phase 1/2 dose-expansion study (NCT03460977) investigating the combination of mevrometostat with enzalutamide and androgen deprivation therapy in patients with mCRPC.[6]
The dose-expansion portion of this study enrolled patients with mCRPC who had previously received abiraterone, with evidence of disease progression per modified Prostate Cancer Working Group 3 criteria.[2]
Key efficacy results
In the randomized dose-expansion study, the combination of mevrometostat (1,250 mg twice daily on an empty stomach) plus enzalutamide demonstrated:
- 49% relative reduction in the rate of progression or death
- Approximately 8-month improvement in median radiographic progression-free survival (rPFS)
- Hazard ratio of 0.51 (90% CI: 0.28–0.95)[7]
The median radiographic progression-free survival was 14.3 months with the combination therapy compared to 6.2 months with enzalutamide alone.[8]
Phase III trials
Based on promising phase I/II results, Pfizer has initiated multiple phase 3 clinical trials:
MEVPRO-1 study
The MEVPRO-1 study (NCT06551324) is a randomized phase 3 trial evaluating mevrometostat in combination with enzalutamide versus physician’s choice of therapy in patients with mCRPC previously treated with abiraterone acetate.[9][10]
- Study design: Randomized 1:1 to receive mevrometostat (875 mg twice daily with food) plus enzalutamide (160 mg daily) versus physician’s choice of enzalutamide or docetaxel
- Target enrollment: Approximately 600 patients
- Primary endpoint: Blinded independent central review-assessed rPFS per RECIST 1.1 and PCWG3 criteria
- Key secondary endpoint: Overall survival
MEVPRO-2 study
The MEVPRO-2 study (NCT06629779) is evaluating mevrometostat plus enzalutamide in androgen receptor pathway inhibitor (ARPI)-naïve patients with mCRPC.[11][12]
Additional development
Pfizer has also initiated phase 3 trials evaluating mevrometostat plus enzalutamide in first-line metastatic castration-sensitive prostate cancer.[8][13]
Safety profile
The most common adverse events considered related to mevrometostat treatment include:
Dose optimization studies found that mevrometostat 875 mg twice daily with food showed similar efficacy and better safety compared to the 1,250 mg dose on an empty stomach.[15]
Pharmacokinetics
Based on safety and pharmacokinetic findings from phase 1 trials, mevrometostat 875 mg twice daily with food was selected as the recommended dose for phase 3 clinical development in combination with enzalutamide.[16]
Regulatory status
As of 2025, mevrometostat remains an investigational agent under clinical development by Pfizer. The drug has not received regulatory approval from the Food and Drug Administration (FDA), European Medicines Agency (EMA), or other regulatory authorities.
See also
- Polycomb repressive complex 2
- Tazemetostat (approved EZH2 inhibitor)
- Prostate cancer
- Enzalutamide
References
- “Mevrometostat (PF-06821497)”. Pfizer Oncology Development. Retrieved 11 September 2025.
- Schweizer MT, Calvo M, Moreno V, Mellado B, Castellano D, Spira AI, et al. (2025). “Mevrometostat (PF-06821497), an enhancer of zeste homolog 2 (EZH2) inhibitor, in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC): A randomized dose-expansion study”. Journal of Clinical Oncology. 43 (5_suppl) LBA138. doi:10.1200/JCO.2025.43.5_suppl.LBA138.
- Schweizer MT, Penkov K, Choudhury AD, Calvo E, Frank RC, Liu L, et al. (2024). “Phase 1 trial of mevrometostat (PF-06821497), a potent and selective inhibitor of enhancer of zeste homolog 2 (EZH2), in castration-resistant prostate cancer (CRPC)”. Journal of Clinical Oncology. 42 (16_suppl): 5061. doi:10.1200/JCO.2024.42.16_suppl.5061.
- “SUO 2024: Mevrometostat (PF-06821497) in Combination with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer Previously Treated with Abiraterone Acetate”. UroToday. Retrieved 11 September 2025.
- “Mevrometostat and enzalutamide in mCRPC: gene expression and EZH2 modulation”. VJ Oncology. 17 February 2025. Retrieved 11 September 2025.
- Pfizer (4 September 2025). A PHASE I DOSE ESCALATION AND EXPANDED COHORT STUDY OF PF 06821497 (MEVROMETOSTAT) IN THE TREATMENT OF ADULT PATIENTS WITH RELAPSED/REFRACTORY SMALL CELL LUNG CANCER (SCLC), CASTRATION RESISTANT PROSTATE CANCER (CRPC) AND FOLLICULAR LYMPHOMA (FL) (Report). clinicaltrials.gov.
- “ASCO GU 2025: Mevrometostat (PF-06821497), an EZH2 Inhibitor, in Combination with Enzalutamide in Patients with mCRPC”. UroToday. Retrieved 11 September 2025.
- “Mevrometostat/enzalutamide combo shows rPFS benefit in mCRPC”. Urology Times. 21 February 2025. Retrieved 11 September 2025.
- Agarwal N, Schweizer MT, Castro E, Azad A, George DJ, Chakrabarti J, et al. (2025). “Mevrometostat (PF-06821497) in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate: The phase 3, randomized MEVPRO-1 study”. Journal of Clinical Oncology. 43 (5_suppl) TPS288. doi:10.1200/JCO.2025.43.5_suppl.TPS288.
- Pfizer (4 September 2025). A PHASE 3, RANDOMIZED, OPEN-LABEL STUDY OF PF-06821497 (MEVROMETOSTAT) IN COMBINATION WITH ENZALUTAMIDE COMPARED WITH ENZALUTAMIDE OR DOCETAXEL IN PARTICIPANTS WITH METASTATIC CASTRATION RESISTANT PROSTATE CANCER PREVIOUSLY TREATED WITH ABIRATERONE ACETATE (MEVPRO-1) (Report). clinicaltrials.gov.
- “ASCO GU 2025: Mevrometostat (PF-06821497) in Combination With Enzalutamide for ARPI-Naïve Patients With mCRPC: The Phase 3, Randomized MEVPRO-2 Trial”. UroToday. Retrieved 11 September 2025.
- Pfizer (4 September 2025). A PHASE 3, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED STUDY OF PF-06821497 (MEVROMETOSTAT) WITH ENZALUTAMIDE IN METASTATIC CASTRATION RESISTANT PROSTATE CANCER (MEVPRO-2) (Report). clinicaltrials.gov.
- Pfizer (4 September 2025). A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Mevrometostat (PF-06821497) With Enzalutamide in Metastatic Castration-Sensitive Prostate Cancer (MEVPRO-3) (Report). clinicaltrials.gov.
- “ASCO 2025: Mevrometostat in Combination with Enzalutamide in Patients with mCRPC Previously Treated with Abiraterone Acetate”. UroToday. Retrieved 11 September 2025.
- “Mevrometostat Plus Enzalutamide Improves rPFS vs Enzalutamide in Metastatic CRPC”. OncLive. 21 February 2025. Retrieved 11 September 2025.
- “ASCO 2025: Safety and Pharmacokinetics of Mevrometostat in Combination with Enzalutamide in Patients with mCRPC”. UroToday. Retrieved 11 September 2025.
| Clinical data | |
|---|---|
| Other names | PF-06821497 |
| Identifiers | |
| IUPAC name | |
| CAS Number | 1844849-10-0 |
| PubChem CID | 118572065 |
| IUPHAR/BPS | 10516 |
| DrugBank | DB14799 |
| ChemSpider | 65321668 |
| UNII | S4L4MM20B6 |
| KEGG | D12845 |
| ChEMBL | ChEMBL4080228 |
| PDB ligand | CJD (PDBe, RCSB PDB) |
| Chemical and physical data | |
| Formula | C22H24Cl2N2O5 |
| Molar mass | 467.34 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
/////////mevrometostat, enhancer of zeste homolog 2 (EZH2) inhibitor, antineoplastic, PF-06821497, PF 06821497, S4L4MM20B6
#mevrometostat, #enhancer of zeste homolog 2 (EZH2) inhibitor, #antineoplastic, #PF-06821497, #PF 06821497, #S4L4MM20B6
Luvometinib
Luvometinib
CAS 2739690-43-6
MF C26H22F2IN5O4S MW665.5 g/mol
CHINA 2025, APPROVALS 2025
N-[3-[6-cyclopropyl-3-fluoro-4-(2-fluoro-4-iodoanilino)-1-methyl-2,5-dioxopyrido[2,3-d]pyridazin-8-yl]phenyl]cyclopropanesulfonamide
N-{3-[6-cyclopropyl-3-fluoro-4-(2-fluoro-4-iodoanilino)-1-methyl-2,5-dioxo-1,2,5,6-tetrahydropyrido[2,3-
d]pyridazin-8-yl]phenyl}cyclopropanesulfonamide
mitogen-activated protein kinase (MEK) inhibitor, antineoplastic, FCN 159, FCN-159, B2DYT4V89X
Luvometinib is a drug for the treatment of various types of cancer. It is a selective, orally administered inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/MEK2), developed by Fosun Pharma for the treatment of rare malignancies, especially those driven by abnormal abnormal mitogen-activated protein kinase (MAPK) activation.[1][2]
In May 2025, it was approved in China for the treatment of histiocytic neoplasms such as Langerhans cell histiocytosis (LCH) and the genetic disease neurofibromatosis type 1 (NF1).[2]
Luvometinib is an orally bioavailable inhibitor of mitogen-activated protein kinase kinase (MAP2K, MAPK/ERK kinase, or MEK) 1 and 2, with potential antineoplastic activity. Upon administration, luvometinib selectively binds to and inhibits the activity of MEK1 and MEK2, preventing the activation of MEK1/2-dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK1/2 are dual-specificity threonine/tyrosine kinases that play key roles in the activation of the RAS/RAF/MEK/ERK pathway that regulates cell growth. This pathway is often dysregulated in a variety of tumor cell types through BRAF, KRAS and NRAS mutations.
Luvometinib is a small molecule drug. The usage of the INN stem ‘-tinib’ in the name indicates that Luvometinib is a tyrosine kinase inhibitor. Luvometinib is under investigation in clinical trial NCT07004075 (FCN-159 Monotherapy Versus Chemotherapy by Investigator’s Choice in Pediatric Low-grade Glioma Patients With BRAF Alteration). Luvometinib has a monoisotopic molecular weight of 665.04 Da.
SYN
Example 8
N-(3-(6-allyl-3-ƒluoro-4-(2-ƒluoro-4-iodophenylamino)-1-methyl-2,5-dioxo-1,2,5,6- tetrahydropyrido[2,3-d]pyridazin-8-yl)phenyl)cyclopropanesulƒonamide (8)
The title compound 8 was prepared following the same procedure as described for Example 5 by substituting methanesulfonyl chloride with cyclopropanesulfonyl chloride. MS-ESI (m/z): 666 [M + 1]+.
PAT
Example 8
N-(3-(6-cyclopropyl-3-fluoro-4-(2-fluoro-4-iodophenylamino)-1-methyl-2,5-dioxo-1,2,5,6-tetrahydropyrido[2,3-d]pyridazin-8-yl)phenyl)cyclopropanesulfonamide (8)
[0136] The title compound 8 was prepared following the same procedure as described for Example 5 by substituting methanesulfonyl chloride with cyclopropanesulfonyl chloride. MS-ESI (m/z): 666 [M + 1] +.
PAT
- Protein kinase inhibitorsPublication Number: CN-106905316-BPriority Date: 2013-04-18Grant Date: 2021-06-01
- Certain protein kinase inhibitorsPublication Number: EP-2986611-B1Priority Date: 2013-04-18Grant Date: 2019-02-06
- Certain protein kinase inhibitorsPublication Number: US-10022374-B2Priority Date: 2013-04-18Grant Date: 2018-07-17
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
References
- Cheng Y, Tian H (2017). “Current Development Status of MEK Inhibitors”. Molecules. 22 (10). Basel, Switzerland: 1551. doi:10.3390/molecules22101551. PMC 6151813. PMID 28954413.
- Keam SJ (2025). “Luvometinib: First Approval”. Drugs. 85 (9): 1177–1183. doi:10.1007/s40265-025-02217-6. PMID 40751881.
| Clinical data | |
|---|---|
| Trade names | 复迈宁 (Fu Mainin) |
| Other names | FCN-159 |
| Routes of administration | Oral |
| Identifiers | |
| IUPAC name | |
| CAS Number | 2739690-43-6 |
| PubChem CID | 135210935 |
| IUPHAR/BPS | 13495 |
| UNII | B2DYT4V89X |
| Chemical and physical data | |
| Formula | C26H22F2IN5O4S |
| Molar mass | 665.45 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
//////////luvometinib, CHINA 2025, APPROVALS 2025, antineoplastic, FCN 159, FCN-159, B2DYT4V89X, ANAX, PTFEON, ADVECT, BLUE JET
ADVERTISEMENT
ANAX LABORATORIES
WEBSITE https://www.anaxlab.com/
Discovery Solutions, Supporting the chemistry needs of clients in the Medical, Analytical and Bio Sciences
Development Solutions, Developing from Lab scale to PR&D, Kilo Scale-ups and Commercial Scales
SEE MORE………Integrated Solutions, Manufacturing Solutions, Products,
Can’t Find? Let’s Connect
Phone : +91 897704 2010 / +91 9177075735, Email : info@anaxlab.com
ADVERTISEMENT
Advect Process Systems Ltd.
ADVECT PROCESS SYSTEMS CANADA LTD
51 Beechwood Rd., Cambridge, ON Canada N1S 3S1, Call Now +1 306 850 6737, Mail Now, ask@advectprocess.com
ADVERTISEMENT
BLUE JET HEALTHCARE LTD, https://bluejethealthcare.com
Looking for a Reliable SNAC Manufacturer? Let’s Talk.
At Blue Jet Healthcare Ltd, we specialize in the scalable, high-purity production of SNAC—a critical excipient powering the next generation of oral peptide therapeutics.
With increasing demand for SNAC across global pharma pipelines, choosing the right manufacturing partner is essential. Quality, timelines, and consistency matter.
Phone No. +91 (22) 22075307 / +91 (22) 22071691
Business Development/ Contract Manufacturing: marketing1@bluejethealthcare.com, madhu.gautam71@gmail.com
Lutetium (177Lu) tezuvotide tetraxetan
Lutetium (177Lu) tezuvotide tetraxetan
CAS2613239-73-7
MF C60H92F177LuN12O23Si , 1573.5 g/mol
2-[4-[2-[[(2R)-1-[[(1R)-1-carboxy-5-[[4-[[(4R)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(1S)-1,3-dicarboxypropyl]carbamoylamino]butanoyl]amino]butyl]amino]-4-oxobutanoyl]amino]pentyl]amino]-3-[[4-[ditert-butyl(fluoro)silyl]benzoyl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-7,10-bis(carboxylatomethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetate;lutetium-177(3+)
antineoplastic, 177LU-RHPSMA-10.1, RHPSMA-10.1 LUTETIUM LU-177, FJ9Z7Y8MRW
Lutetium (177Lu) tezuvotide tetraxetan ($^{177}$Lu-rhPSMA-10.1) is an experimental radioligand therapy, developed by Bracco, that targets prostate-specific membrane antigen (PSMA) to treat metastatic castration-resistant prostate cancer. It uses a radiohybrid (rh) PSMA molecule, designed to have high binding affinity to PSMA-positive cancer cells and deliver targeted beta-minus radiation.
Key details:
- Mechanism: It binds to PSMA-expressing cells, leading to DNA damage and tumor cell death.
- Target: Prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer.
- Distinction: It is distinct from the FDA-approved ${177}$Lu-vipivotide tetraxetan (Pluvicto), though it is part of the same class of PSMA-targeted radiopharmaceutical agents.
- Status: It has been tested in clinical trials as a potential therapy for advanced prostate cancer, including studies evaluating its efficacy and safety.
It is important to distinguish between the various PSMA-targeted agents, such as vipivotide tetraxetan, which is approved for use.
Lutetium Lu 177 Tezuvotide Tetraxetan is a radioconjugate composed of PSMA-10.1, a prostate-specific membrane antigen (PSMA)-targeting ligand and radiolabeled with the beta-emitting radioisotope lutetium Lu 177 (177Lu), with potential antineoplastic activity against PSMA-expressing tumor cells. Upon intravenous administration, lutetium Lu 177 tezuvotide tetraxetan targets and binds to PSMA-expressing tumor cells. Upon binding, PSMA-expressing tumor cells are destroyed by 177Lu through the specific delivery of beta particle radiation. PSMA, a tumor-associated antigen (TAA) and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells as well as a variety of other solid tumors.
An open-label, multicentre, integrated Phase 1 & 2 study to evaluate the safety, tolerability, radiation dosimetry and anti-tumour activity of Lutetium (177Lu) rhPSMA-10.1 injection in men with metastatic castrate-resistant prostate cancer
EudraCT: 2022-002407-37
Phase: Phase 2
Status: Trial now transitioned
Date: 2023-05-22
PAT
https://patents.google.com/patent/WO2024121722A1/en
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
//////////////lutetium (177Lu) tezuvotide tetraxetan, antineoplastic, 177LU-RHPSMA-10.1, RHPSMA-10.1 LUTETIUM LU-177, FJ9Z7Y8MRW
Istisociclib
Istisociclib
KB 130742
CAS 2416873-83-9
MF C16H25N5, 287.40 g/mol
trans-(1S,3S)-3-N-(5-pentan-3-ylpyrazolo[1,5-a]pyrimidin-7-yl)cyclopentane-1,3-diamine
- (1S,3S)-N1-[5-(1-Ethylpropyl)pyrazolo[1,5-a]pyrimidin-7-yl]-1,3-cyclopentanediamine
- 1,3-Cyclopentanediamine, N1-[5-(1-ethylpropyl)pyrazolo[1,5-a]pyrimidin-7-yl]-, (1S,3S)-
(1S,3S)-N1-[5-(pentan-3-yl)pyrazolo[1,5-a]pyrimidin-7-yl]cyclopentane-1,3-diamine
cyclin-dependent kinase (CDK) inhibitor, antineoplastic, KB-0742, 2416873-83-9, KB 0742, F7J6KSY5I8, UB-18422, KB-130742, KB 00130742
Istisociclib is a small molecule drug. The usage of the INN stem ‘-ciclib’ in the name indicates that Istisociclib is a cyclin dependant kinase inhibitor. Istisociclib is under investigation in clinical trial NCT04718675 (A Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors Including Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC)). Istisociclib has a monoisotopic molecular weight of 287.21 Da.
Istisociclib is an orally bioavailable, selective inhibitor of the serine/threonine cyclin-dependent kinase 9 (CDK9), the catalytic subunit of the RNA polymerase II (RNA Pol II) elongation factor positive transcription elongation factor b (PTEF-b; PTEFb), with potential antineoplastic activity. Upon oral administration, istisociclib targets, binds to and blocks the phosphorylation and kinase activity of CDK9, thereby preventing PTEFb-mediated activation of RNA Pol II, leading to the inhibition of gene transcription of various anti-apoptotic proteins and oncogenic transcription factors including MYC and androgen receptor (AR). This induces cell cycle arrest and apoptosis and prevents tumor cell proliferation. CDK9 regulates elongation of transcription through phosphorylation of RNA Pol II at serine 2 (p-Ser2-RNAPII), and is an important cofactor for various oncogenic transcription factors. It is upregulated in various tumor cell types and plays a key role in the regulation of Pol II-mediated transcription of anti-apoptotic proteins. Tumor cells are dependent on anti-apoptotic proteins for their survival.
ISTISOCICLIB is a small molecule drug with a maximum clinical trial phase of II and has 1 investigational indication.
A Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors Including Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC)
CTID: NCT04718675
Phase: Phase 1/Phase 2
Status: Terminated
Date: 2025-02-17
REF
- Discovery of KB-0742, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of CDK9 for MYC-Dependent CancersPublication Name: Journal of Medicinal ChemistryPublication Date: 2023-11-15PMCID: PMC10726352PMID: 37967851DOI: 10.1021/acs.jmedchem.3c01233
- CDK9 inhibitors in cancer researchPublication Name: RSC Medicinal ChemistryPublication Date: 2022-06-22PMCID: PMC9215160PMID: 35814933DOI: 10.1039/d2md00040g
- From Structure Modification to Drug Launch: A Systematic Review of the Ongoing Development of Cyclin-Dependent Kinase Inhibitors for Multiple Cancer TherapyPublication Name: Journal of Medicinal ChemistryPublication Date: 2022-04-29PMID: 35485642DOI: 10.1021/acs.jmedchem.1c02064
- Lessons Learned from Past Cyclin-Dependent Kinase Drug Discovery EffortsPublication Name: Journal of Medicinal ChemistryPublication Date: 2022-03-02PMID: 35235745DOI: 10.1021/acs.jmedchem.1c02190
PAT
(lS,3S)-N1-(5-(pentan-3-yl)pyrazolo[l,5-a]pyrimidin-7-yl)cyclopentane-l,3-diamine is a pharmaceutically active compound that has been studied for various uses, such as for the treatment of cancer. As used herein, the term “Compound A” is used to refer to both the free base and salt forms of (lS,3S)-N1-(5-(pentan-3-yl)pyrazolo[l,5-a]pyrimidin-7-yl)cyclopentane-l,3-diamine. The free base of Compound A has the CAS number of 2416873-83-9 and structure of formula (I):
SYN
Example 35: (1S,3S)-N3-[5-(1-ethylpropyl)pyrazolo[1,5-a]pyrimidin-7-yl]cyclopentane-1,3-diamine (35)
2-Ethylbutanoic acid (7.5 g, 64.57 mmol) was dissolved in THF (150 mL) and cooled to 0 °C. Within 20 min CDI (16.23 g, 100.08 mmol) was added portion-wise. The reaction warmed to room temp (rt) and the mixture was stirred at rt overnight (Solution A). In another flask MgCl2 (6.14 g, 64.57 mmol) and potassium 3-ethoxy-3-oxo-propanoate (17 g, 100.1 mmol) were mixed with THF (150 mL) and stirred under argon overnight at 50 °C. The resultant white suspension was cooled to rt and solution A was added dropwise over 10 min and the reaction mixture (RM) was stirred for 16h at room temperature. After several minutes a sticky, amorphous solid appeared whereupon after several hours the reaction mixture became homogenous in appearance. The RM was concentrated to about a third, taken up in half sat. potassium bisulphate solution and extracted twice with ethyl acetate. The organic layers were subsequently washed with a sat. sodium bicarbonate solution, combined, dried over anhydrous sodium sulfate, filtered and evaporated. Purification by column chromatography gave ethyl 4-ethyl-3-oxo-hexanoate (4.3 g, 23.087 mmol, 35.8% yield) as a transparent liquid. The RM was monitored by TLC (10% EA in Hex, Product Rf=0.6, SM Rf=0.1).
Step 2
To a suspension of ethyl 4-ethyl-3-oxo-hexanoate (4.4 g, 23.62 mmol) in acetic acid (11 mL) at 70 °C was added 1H-pyrazol-5-amine (4.71 g, 56.7 mmol) in two portions (the second portion was added after 2 hours of stirring the first portion) over a 4 hour period. Upon consumption of SM as indicated by TLC, the reaction was cooled to rt and the solvent was evaporated in a rotary evaporator. The residue was treated with ethyl acetate and filtered to give 5-(1-ethylpropyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one (3.7 g, 17.7 mmol, 74.9% yield) as an off-white solid. The reaction mixture was monitored by TLC (5% MeOH in DCM, Product Rf=0.3, SM Rf=0.8).
Step 3
A stirred solution of 5-(1-ethylpropyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one (3.7 g, 18.03 mmol) in POCl3 (33.7 mL, 360.52 mmol) was heated to reflux for 4 hours. The reaction mixture was cooled to room temperature, excess reagent was evaporated in a rotary evaporator, and the residue was treated with ice-water. The chlorinated product was extracted from aqueous mixture by DCM. The organic layer was separated, dried over anhydrous Na2SO4, filtered and purified by column chromatography to give 7- chloro-5-(1-ethylpropyl)pyrazolo[1,5-a]pyrimidine (3.1 g, 13.9 mmol, 76.9% yield) as a light yellow liquid. The reaction mixture was monitored by TLC (20% EA in Hex, Product Rf=0.6, SM Rf=0.1).
To a stirred solution 7-chloro-5-(1-ethylpropyl)pyrazolo[1,5-a]pyrimidine (2.3 g, 10.28 mmol), tert-Butyl ((1S,3S)-3-aminocyclopentyl)carbamate (2.27 g, 11.31 mmol) and K2CO3 (4.26 g, 30.84 mmol) in MeCN (20 mL) were heated to reflux for 16 hours. The reaction mixture was filtered, concentrated under reduced pressure and purified by column chromatography, eluent 30% EA in hexane to give tert-butyl N-[(1S,3S)-3-[[5-(1-ethylpropyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino]cyclopentyl]carbamate (4.5 g, 11.6 mmol, 112.8% yield) as an off-white solid. The reaction mixture was monitored by TLC (40% EA in Hex, Product Rf=0.5, SM Rf=0.7).
Step 5
To tert-butyl N-[(1 S,3S)-3-[[5-(l-ethylpropyl)pyrazolo[l,5-a]pyrimidin-7-yl]amino]cyclopentyl]carbamate (1.0 g, 2.58 mmol) in l,4-Dioxane (0.2 mL), 4 M HC1 in Dioxane (3.22 mL, 12.9 mmol) was added and stirred at room temperature for 4 hours. The reaction mixture was evaporated in vacuo, triturated with pentane and lyophilized from MeCN:H20 to give [(lS,3S)-3-[[5-(l-ethylpropyl)pyrazolo[l,5-a]pyrimidin-4-ium-7-yl]amino]cyclopentyl]ammonium dichloride (0.9 g, 2.5 mmol, 96.8% yield) as a pale-yellow sticky solid. The reaction mixture was monitored by TLC ( 100% EA, Product Rf=0.l, SM Rf=0.8). 1H NMR (400 MHz, DMSO-d6) d 15.00 (s, 1H), 9.93-9.86 (m, 1H), 8.51 (s, 3H), 8.30 (s, 1H), 6.84 (s, 1H), 6.58 (s, 1H), 4.95 (q, J = 7.8 Hz, 1H), 3.77- 3.66 (m, 1H), 2.84-2.71 (m, 1H), 2.29-2.05 (m, 4H), 1.94-1.63 (m, 6H), 0.81 (t, J = 7.4 Hz, 6H). LC-MS (m/z 287.21, found 288.0 [M+H+])
Step 6
To [(1S,3S)-3-[[5-(l-ethylpropyl)pyrazolo[I,5-a]pyrimidin-4-ium-7-yl]amino]cyclopentyl]ammonium-di chloride (0.2 g, 0.5600 mmol) in aq. NH3 (4.0 mL, 0.56 mmol) was added and stirred at room temperature for 4 hours. The reaction mixture was evaporated in vacuo, triturated with pentane and lyophilized from MeCN:H20 to give (lS,3S)-N3-[5-(l-ethylpropyl)pyrazolo[l,5-a]pyrimidin-7-yl]cyclopentane-l,3-diamine (140 mg, 0.49 mmol, 87.8% yield) as a pale-yellow sticky solid. The reaction mixture was monitored by TLC (100% EA, Product Rf=0.1, SM Rf=0.8). 1H NMR (400 MHz, DMSO-d6) d 7.95 (d, J = 2.2 Hz, 1H), 6.86 (s, 1H), 6.29 (d, J = 2.2 Hz, 1H), 5.95 (s, 1H), 4.31-4.19 (m, 1H), 3.57-3.44 (m, 1H), 2.52-2.44 (m, 1H), 2.36-2.22 (m, 1H),
2.09–1.79 (m, 3H), 1.80–1.59 (m, 5H), 1.58–1.24 (m, 3H), 0.83 (t, J = 7.4 Hz, 6H). LC-MS (m/z 287.21, found 288.5 [M+H+]).
PAT
- Compounds, compositions and methods for modulating CDK9 activityPublication Number: CN-112996790-BPriority Date: 2018-10-30Grant Date: 2023-11-03
- Compounds, compositions, and methods for modulating cdk9 activityPublication Number: US-2024132506-A1Priority Date: 2018-10-30
- Compounds, Compositions, and Methods for Modulating CDK9 ActivityPublication Number: US-2020131189-A1Priority Date: 2018-10-30
- Compounds, compositions, and methods for modulating cdk9 activityPublication Number: US-2022002305-A1Priority Date: 2018-10-30
- Compounds, compositions, and methods for modulating cdk9 activityPublication Number: EP-3873911-A1Priority Date: 2018-10-30
- Substituted pyrazolo[1,5-a]pyrimidines for modulating CDK9 activityPublication Number: US-11845754-B2Priority Date: 2018-10-30Grant Date: 2023-12-19
- Substituted pyrazolo[1,5-a]pyrimidines for modulating CDK9 activityPublication Number: US-11155560-B2Priority Date: 2018-10-30Grant Date: 2021-10-26
- Compounds and methods for modulating cdk9 activityPublication Number: EP-4240422-A1Priority Date: 2020-11-05
- Compounds and methods for modulating cdk9 activityPublication Number: WO-2022098843-A1Priority Date: 2020-11-05
- Compounds and methods for modulating cdk9 activityPublication Number: US-2025188084-A1Priority Date: 2020-11-05
- Chimeric degraders of cyclin-dependent kinase 9 and uses thereofPublication Number: WO-2021216828-A1Priority Date: 2020-04-24
- Chimeric degraders of cyclin-dependent kinase 9 and uses thereofPublication Number: US-2023158159-A1Priority Date: 2020-04-24
- Polymorphic and salt forms of (ls,3s)-n-(5-(pentan-3- yl)pyrazolo[l,5-a]pyrimidin-7-yl)cyclopentane-l,3-diaminePublication Number: EP-4436569-A1Priority Date: 2021-11-24
- Polymorphs and salt forms of (1S,3S)-N1-(5-(pentan-3-yl)pyrazolo[1,5-A]pyrimidin-7-yl)cyclopentane-1,3-diaminePublication Number: KR-20240110634-APriority Date: 2021-11-24
- Compositions and methods for enhanced protein productionPublication Number: EP-4412621-A2Priority Date: 2021-09-22
- Compositions and methods for enhanced protein productionPublication Number: US-2024252688-A1Priority Date: 2021-09-22
- Compositions and methods for enhanced protein productionPublication Number: WO-2023056202-A2Priority Date: 2021-09-22
- A cdk9 inhibitor for use in the treatment of cancer in a subject having an asxl1 mutationPublication Number: WO-2025217597-A1Priority Date: 2024-04-12
- Polymorphic and salt forms of (1s,3s)-n1-(5-(pentan-3- yl)pyrazolo[1,5-a]pyrimidin-7-yl)cyclopentane-1,3-diaminePublication Number: WO-2023096922-A8Priority Date: 2021-11-24
- Polymorphic and salt forms of (ls,3s)-n1-(5-(pentan-3- yl)pyrazolo[l,5-a]pyrimidin-7-yl)cyclopentane-l,3-diaminePublication Number: WO-2023096922-A1Priority Date: 2021-11-24
- Polymorphic and salt forms of (1s,3s)-n1-(5-(pentan-3-yl)pyrazolo[1,5-a]pyrimidin-7-yl) cyclopentane-1,3-diaminePublication Number: US-2025059193-A1Priority Date: 2021-11-24
- Polymorphic forms and salt forms of (1S,3S)-N1-(5-(pentan-3-yl)pyrazolo[1,5-a]pyrimidin-7-yl)cyclopentane-1,3-diaminePublication Number: CN-118678952-APriority Date: 2021-11-24
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
//////istisociclib, cyclin-dependent kinase (CDK) inhibitor, antineoplastic, KB-0742, 2416873-83-9, KB 0742, F7J6KSY5I8, UB-18422, KB-130742, KB 00130742
Istisociclib
Istisociclib
KB 130742
CAS 2416873-83-9
MF C16H25N5, 287.40 g/mol
trans-(1S,3S)-3-N-(5-pentan-3-ylpyrazolo[1,5-a]pyrimidin-7-yl)cyclopentane-1,3-diamine
- (1S,3S)-N1-[5-(1-Ethylpropyl)pyrazolo[1,5-a]pyrimidin-7-yl]-1,3-cyclopentanediamine
- 1,3-Cyclopentanediamine, N1-[5-(1-ethylpropyl)pyrazolo[1,5-a]pyrimidin-7-yl]-, (1S,3S)-
(1S,3S)-N1-[5-(pentan-3-yl)pyrazolo[1,5-a]pyrimidin-7-yl]cyclopentane-1,3-diamine
cyclin-dependent kinase (CDK) inhibitor, antineoplastic, KB-0742, 2416873-83-9, KB 0742, F7J6KSY5I8, UB-18422, KB-130742, KB 00130742
Istisociclib is a small molecule drug. The usage of the INN stem ‘-ciclib’ in the name indicates that Istisociclib is a cyclin dependant kinase inhibitor. Istisociclib is under investigation in clinical trial NCT04718675 (A Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors Including Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC)). Istisociclib has a monoisotopic molecular weight of 287.21 Da.
Istisociclib is an orally bioavailable, selective inhibitor of the serine/threonine cyclin-dependent kinase 9 (CDK9), the catalytic subunit of the RNA polymerase II (RNA Pol II) elongation factor positive transcription elongation factor b (PTEF-b; PTEFb), with potential antineoplastic activity. Upon oral administration, istisociclib targets, binds to and blocks the phosphorylation and kinase activity of CDK9, thereby preventing PTEFb-mediated activation of RNA Pol II, leading to the inhibition of gene transcription of various anti-apoptotic proteins and oncogenic transcription factors including MYC and androgen receptor (AR). This induces cell cycle arrest and apoptosis and prevents tumor cell proliferation. CDK9 regulates elongation of transcription through phosphorylation of RNA Pol II at serine 2 (p-Ser2-RNAPII), and is an important cofactor for various oncogenic transcription factors. It is upregulated in various tumor cell types and plays a key role in the regulation of Pol II-mediated transcription of anti-apoptotic proteins. Tumor cells are dependent on anti-apoptotic proteins for their survival.
ISTISOCICLIB is a small molecule drug with a maximum clinical trial phase of II and has 1 investigational indication.
A Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors Including Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC)
CTID: NCT04718675
Phase: Phase 1/Phase 2
Status: Terminated
Date: 2025-02-17
REF
- Discovery of KB-0742, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of CDK9 for MYC-Dependent CancersPublication Name: Journal of Medicinal ChemistryPublication Date: 2023-11-15PMCID: PMC10726352PMID: 37967851DOI: 10.1021/acs.jmedchem.3c01233
- CDK9 inhibitors in cancer researchPublication Name: RSC Medicinal ChemistryPublication Date: 2022-06-22PMCID: PMC9215160PMID: 35814933DOI: 10.1039/d2md00040g
- From Structure Modification to Drug Launch: A Systematic Review of the Ongoing Development of Cyclin-Dependent Kinase Inhibitors for Multiple Cancer TherapyPublication Name: Journal of Medicinal ChemistryPublication Date: 2022-04-29PMID: 35485642DOI: 10.1021/acs.jmedchem.1c02064
- Lessons Learned from Past Cyclin-Dependent Kinase Drug Discovery EffortsPublication Name: Journal of Medicinal ChemistryPublication Date: 2022-03-02PMID: 35235745DOI: 10.1021/acs.jmedchem.1c02190
PAT
(lS,3S)-N1-(5-(pentan-3-yl)pyrazolo[l,5-a]pyrimidin-7-yl)cyclopentane-l,3-diamine is a pharmaceutically active compound that has been studied for various uses, such as for the treatment of cancer. As used herein, the term “Compound A” is used to refer to both the free base and salt forms of (lS,3S)-N1-(5-(pentan-3-yl)pyrazolo[l,5-a]pyrimidin-7-yl)cyclopentane-l,3-diamine. The free base of Compound A has the CAS number of 2416873-83-9 and structure of formula (I):
SYN
Example 35: (1S,3S)-N3-[5-(1-ethylpropyl)pyrazolo[1,5-a]pyrimidin-7-yl]cyclopentane-1,3-diamine (35)
2-Ethylbutanoic acid (7.5 g, 64.57 mmol) was dissolved in THF (150 mL) and cooled to 0 °C. Within 20 min CDI (16.23 g, 100.08 mmol) was added portion-wise. The reaction warmed to room temp (rt) and the mixture was stirred at rt overnight (Solution A). In another flask MgCl2 (6.14 g, 64.57 mmol) and potassium 3-ethoxy-3-oxo-propanoate (17 g, 100.1 mmol) were mixed with THF (150 mL) and stirred under argon overnight at 50 °C. The resultant white suspension was cooled to rt and solution A was added dropwise over 10 min and the reaction mixture (RM) was stirred for 16h at room temperature. After several minutes a sticky, amorphous solid appeared whereupon after several hours the reaction mixture became homogenous in appearance. The RM was concentrated to about a third, taken up in half sat. potassium bisulphate solution and extracted twice with ethyl acetate. The organic layers were subsequently washed with a sat. sodium bicarbonate solution, combined, dried over anhydrous sodium sulfate, filtered and evaporated. Purification by column chromatography gave ethyl 4-ethyl-3-oxo-hexanoate (4.3 g, 23.087 mmol, 35.8% yield) as a transparent liquid. The RM was monitored by TLC (10% EA in Hex, Product Rf=0.6, SM Rf=0.1).
Step 2
To a suspension of ethyl 4-ethyl-3-oxo-hexanoate (4.4 g, 23.62 mmol) in acetic acid (11 mL) at 70 °C was added 1H-pyrazol-5-amine (4.71 g, 56.7 mmol) in two portions (the second portion was added after 2 hours of stirring the first portion) over a 4 hour period. Upon consumption of SM as indicated by TLC, the reaction was cooled to rt and the solvent was evaporated in a rotary evaporator. The residue was treated with ethyl acetate and filtered to give 5-(1-ethylpropyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one (3.7 g, 17.7 mmol, 74.9% yield) as an off-white solid. The reaction mixture was monitored by TLC (5% MeOH in DCM, Product Rf=0.3, SM Rf=0.8).
Step 3
A stirred solution of 5-(1-ethylpropyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one (3.7 g, 18.03 mmol) in POCl3 (33.7 mL, 360.52 mmol) was heated to reflux for 4 hours. The reaction mixture was cooled to room temperature, excess reagent was evaporated in a rotary evaporator, and the residue was treated with ice-water. The chlorinated product was extracted from aqueous mixture by DCM. The organic layer was separated, dried over anhydrous Na2SO4, filtered and purified by column chromatography to give 7- chloro-5-(1-ethylpropyl)pyrazolo[1,5-a]pyrimidine (3.1 g, 13.9 mmol, 76.9% yield) as a light yellow liquid. The reaction mixture was monitored by TLC (20% EA in Hex, Product Rf=0.6, SM Rf=0.1).
To a stirred solution 7-chloro-5-(1-ethylpropyl)pyrazolo[1,5-a]pyrimidine (2.3 g, 10.28 mmol), tert-Butyl ((1S,3S)-3-aminocyclopentyl)carbamate (2.27 g, 11.31 mmol) and K2CO3 (4.26 g, 30.84 mmol) in MeCN (20 mL) were heated to reflux for 16 hours. The reaction mixture was filtered, concentrated under reduced pressure and purified by column chromatography, eluent 30% EA in hexane to give tert-butyl N-[(1S,3S)-3-[[5-(1-ethylpropyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino]cyclopentyl]carbamate (4.5 g, 11.6 mmol, 112.8% yield) as an off-white solid. The reaction mixture was monitored by TLC (40% EA in Hex, Product Rf=0.5, SM Rf=0.7).
Step 5
To tert-butyl N-[(1 S,3S)-3-[[5-(l-ethylpropyl)pyrazolo[l,5-a]pyrimidin-7-yl]amino]cyclopentyl]carbamate (1.0 g, 2.58 mmol) in l,4-Dioxane (0.2 mL), 4 M HC1 in Dioxane (3.22 mL, 12.9 mmol) was added and stirred at room temperature for 4 hours. The reaction mixture was evaporated in vacuo, triturated with pentane and lyophilized from MeCN:H20 to give [(lS,3S)-3-[[5-(l-ethylpropyl)pyrazolo[l,5-a]pyrimidin-4-ium-7-yl]amino]cyclopentyl]ammonium dichloride (0.9 g, 2.5 mmol, 96.8% yield) as a pale-yellow sticky solid. The reaction mixture was monitored by TLC ( 100% EA, Product Rf=0.l, SM Rf=0.8). 1H NMR (400 MHz, DMSO-d6) d 15.00 (s, 1H), 9.93-9.86 (m, 1H), 8.51 (s, 3H), 8.30 (s, 1H), 6.84 (s, 1H), 6.58 (s, 1H), 4.95 (q, J = 7.8 Hz, 1H), 3.77- 3.66 (m, 1H), 2.84-2.71 (m, 1H), 2.29-2.05 (m, 4H), 1.94-1.63 (m, 6H), 0.81 (t, J = 7.4 Hz, 6H). LC-MS (m/z 287.21, found 288.0 [M+H+])
Step 6
To [(1S,3S)-3-[[5-(l-ethylpropyl)pyrazolo[I,5-a]pyrimidin-4-ium-7-yl]amino]cyclopentyl]ammonium-di chloride (0.2 g, 0.5600 mmol) in aq. NH3 (4.0 mL, 0.56 mmol) was added and stirred at room temperature for 4 hours. The reaction mixture was evaporated in vacuo, triturated with pentane and lyophilized from MeCN:H20 to give (lS,3S)-N3-[5-(l-ethylpropyl)pyrazolo[l,5-a]pyrimidin-7-yl]cyclopentane-l,3-diamine (140 mg, 0.49 mmol, 87.8% yield) as a pale-yellow sticky solid. The reaction mixture was monitored by TLC (100% EA, Product Rf=0.1, SM Rf=0.8). 1H NMR (400 MHz, DMSO-d6) d 7.95 (d, J = 2.2 Hz, 1H), 6.86 (s, 1H), 6.29 (d, J = 2.2 Hz, 1H), 5.95 (s, 1H), 4.31-4.19 (m, 1H), 3.57-3.44 (m, 1H), 2.52-2.44 (m, 1H), 2.36-2.22 (m, 1H),
2.09–1.79 (m, 3H), 1.80–1.59 (m, 5H), 1.58–1.24 (m, 3H), 0.83 (t, J = 7.4 Hz, 6H). LC-MS (m/z 287.21, found 288.5 [M+H+]).
PAT
- Compounds, compositions and methods for modulating CDK9 activityPublication Number: CN-112996790-BPriority Date: 2018-10-30Grant Date: 2023-11-03
- Compounds, compositions, and methods for modulating cdk9 activityPublication Number: US-2024132506-A1Priority Date: 2018-10-30
- Compounds, Compositions, and Methods for Modulating CDK9 ActivityPublication Number: US-2020131189-A1Priority Date: 2018-10-30
- Compounds, compositions, and methods for modulating cdk9 activityPublication Number: US-2022002305-A1Priority Date: 2018-10-30
- Compounds, compositions, and methods for modulating cdk9 activityPublication Number: EP-3873911-A1Priority Date: 2018-10-30
- Substituted pyrazolo[1,5-a]pyrimidines for modulating CDK9 activityPublication Number: US-11845754-B2Priority Date: 2018-10-30Grant Date: 2023-12-19
- Substituted pyrazolo[1,5-a]pyrimidines for modulating CDK9 activityPublication Number: US-11155560-B2Priority Date: 2018-10-30Grant Date: 2021-10-26
- Compounds and methods for modulating cdk9 activityPublication Number: EP-4240422-A1Priority Date: 2020-11-05
- Compounds and methods for modulating cdk9 activityPublication Number: WO-2022098843-A1Priority Date: 2020-11-05
- Compounds and methods for modulating cdk9 activityPublication Number: US-2025188084-A1Priority Date: 2020-11-05
- Chimeric degraders of cyclin-dependent kinase 9 and uses thereofPublication Number: WO-2021216828-A1Priority Date: 2020-04-24
- Chimeric degraders of cyclin-dependent kinase 9 and uses thereofPublication Number: US-2023158159-A1Priority Date: 2020-04-24
- Polymorphic and salt forms of (ls,3s)-n-(5-(pentan-3- yl)pyrazolo[l,5-a]pyrimidin-7-yl)cyclopentane-l,3-diaminePublication Number: EP-4436569-A1Priority Date: 2021-11-24
- Polymorphs and salt forms of (1S,3S)-N1-(5-(pentan-3-yl)pyrazolo[1,5-A]pyrimidin-7-yl)cyclopentane-1,3-diaminePublication Number: KR-20240110634-APriority Date: 2021-11-24
- Compositions and methods for enhanced protein productionPublication Number: EP-4412621-A2Priority Date: 2021-09-22
- Compositions and methods for enhanced protein productionPublication Number: US-2024252688-A1Priority Date: 2021-09-22
- Compositions and methods for enhanced protein productionPublication Number: WO-2023056202-A2Priority Date: 2021-09-22
- A cdk9 inhibitor for use in the treatment of cancer in a subject having an asxl1 mutationPublication Number: WO-2025217597-A1Priority Date: 2024-04-12
- Polymorphic and salt forms of (1s,3s)-n1-(5-(pentan-3- yl)pyrazolo[1,5-a]pyrimidin-7-yl)cyclopentane-1,3-diaminePublication Number: WO-2023096922-A8Priority Date: 2021-11-24
- Polymorphic and salt forms of (ls,3s)-n1-(5-(pentan-3- yl)pyrazolo[l,5-a]pyrimidin-7-yl)cyclopentane-l,3-diaminePublication Number: WO-2023096922-A1Priority Date: 2021-11-24
- Polymorphic and salt forms of (1s,3s)-n1-(5-(pentan-3-yl)pyrazolo[1,5-a]pyrimidin-7-yl) cyclopentane-1,3-diaminePublication Number: US-2025059193-A1Priority Date: 2021-11-24
- Polymorphic forms and salt forms of (1S,3S)-N1-(5-(pentan-3-yl)pyrazolo[1,5-a]pyrimidin-7-yl)cyclopentane-1,3-diaminePublication Number: CN-118678952-APriority Date: 2021-11-24
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
//////istisociclib, cyclin-dependent kinase (CDK) inhibitor, antineoplastic, KB-0742, 2416873-83-9, KB 0742, F7J6KSY5I8, UB-18422, KB-130742, KB 00130742
Gridegalutamide
Gridegalutamide
CAS 2446929-86-6
MF C41H45F3N8O5S MW818.9 g/mol
2-[(2R)-4-[2-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]ethyl]-2-methylpiperazin-1-yl]-N-[3-[[(3R)-2,6-dioxopiperidin-3-yl]amino]phenyl]acetamide
antiandrogen, antineoplastic, BMS 986365, CC 94676, BMS-986365, CC-94676, CEL 010355,
VA228VR2DI,
Gridegalutamide is an investigational oral androgen receptor (AR) degrader being developed for the treatment of metastatic castration-resistant prostate cancer (mCRPC). It belongs to a class of drugs called proteolysis targeting chimeras (PROTACs), which are designed to selectively degrade specific proteins by hijacking the ubiquitin-proteasome system.[1][2] CC-94676 employs a unique dual mechanism of action, combining AR degradation with AR antagonism, potentially offering advantages over traditional AR inhibitors in overcoming resistance mechanisms.[3] Initially developed by Celgene and now under Bristol Myers Squibb, CC-94676 has demonstrated AR protein degradation and suppression of tumor growth in CRPC mouse models.[2] As of 2024, CC-94676 is being evaluated in phase I clinical trials for patients with mCRPC who have progressed on androgen deprivation therapy and at least one prior secondary hormonal therapy.[1][2]
Gridegalutamide is a small molecule drug. The usage of the INN stem ‘-lutamide’ in the name indicates that Gridegalutamide is a non-steroid antiandrogen. Gridegalutamide is under investigation in clinical trial NCT04428788 (Study to Evaluate the Safety and Tolerability of CC-94676 in Participants With Metastatic Castration-Resistant Prostate Cancer). Gridegalutamide has a monoisotopic molecular weight of 818.32 Da.
GRIDEGALUTAMIDE is a small molecule drug with a maximum clinical trial phase of II (across all indications) and has 3 investigational indications.
Gridegalutamide is an orally bioavailable androgen receptor (AR) degrader, with potential antineoplastic activity. Upon administration, gridegalutamide causes degradation of AR, prevents AR-mediated signaling and inhibits the proliferation of AR-overexpressing tumor cells. AR plays a key role in tumor cell proliferation in castration-resistant prostate cancer (CRPC).
- A Study to Evaluate the Drug Levels, Metabolism and Excretion, and Absolute Bioavailability of BMS-986365 in Healthy Male ParticipantsCTID: NCT06433505Phase: Phase 1Status: CompletedDate: 2025-03-26
- Study to Evaluate the Safety and Tolerability of CC-94676 in Participants With Metastatic Castration-Resistant Prostate CancerCTID: NCT04428788Phase: Phase 1Status: CompletedDate: 2025-12-22
SYN
DRUGHUNTER
https://drughunter.com/molecule/gridegalutamide-bms-986365-cc-94676
PAT
Example 17: 2-((R)-4-(2-(4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2- thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-((2,6- dioxopiperidin-3-yl)amino)phenyl)acetamide hydrochloride
PAT
- Combination therapy with substituted 3- ((3-aminophenyl) amino) piperidine-2, 6-dione compoundsPublication Number: CN-120152718-APriority Date: 2022-11-09
- Combination therapy with substituted 3-((3-aminophenyl)amino)piperidine-2,6-dione compoundsPublication Number: WO-2024102706-A1Priority Date: 2022-11-09
- Substituted 3-((3-aminophenyl)amino)piperidine-2,6-dione compounds, compositions thereof, and methods of treatment therewithPublication Number: US-2020199073-A1Priority Date: 2018-12-19
- Substituted 3-((3-aminophenyl)amino)piperidine-2,6-dione compounds, compositions thereof, and methods of treatment therewithPublication Number: US-11149007-B2Priority Date: 2018-12-19Grant Date: 2021-10-19
- Substituted 3-((3-aminophenyl)amino)piperidine-2,6-dione compounds, compositions thereof, and methods of treatment therewithPublication Number: US-11873283-B2Priority Date: 2018-12-19Grant Date: 2024-01-16
- Substituted 3-((3-aminophenyl)amino)piperidine-2,6-dione compounds, compositions thereof, and methods of treatment therewithPublication Number: US-2024368083-A1Priority Date: 2018-12-19
- Substituted 3-((3-aminophenyl)amino)piperidine-2,6-dione compounds, compositions thereof, and methods of treatment therewithPublication Number: US-12404241-B2Priority Date: 2018-12-19Grant Date: 2025-09-02
- Substituted 3-((3-aminophenyl)amino)piperidine-2,6-dione compounds, compositions thereof, and methods of treatment therewithPublication Number: US-2023002321-A1Priority Date: 2018-12-19
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
ADVERTISEMENT
ANAX LABORATORIES, WEBSITE https://www.anaxlab.com/
Discovery Solutions, Supporting the chemistry needs of clients in the Medical, Analytical and Bio Sciences
Development Solutions, Developing from Lab scale to PR&D, Kilo Scale-ups and Commercial Scales
SEE MORE………Integrated Solutions, Manufacturing Solutions, Products,
Can’t Find? Let’s Connect
Phone : +91 897704 2010 / +91 9177075735, Email : info@anaxlab.com
ADVERTISEMENT
Advect Process Systems Ltd. https://advectprocess.com
ADVECT PROCESS SYSTEMS CANADA LTD
51 Beechwood Rd., Cambridge, ON Canada N1S 3S1, Call Now +1 306 850 6737, Mail Now, ask@advectprocess.com
References
- Salama AK, Trkulja MV, Casanova E, Uras IZ (December 2022). “Targeted Protein Degradation: Clinical Advances in the Field of Oncology”. International Journal of Molecular Sciences. 23 (23) 15440. doi:10.3390/ijms232315440. PMC 9741350. PMID 36499765.
- Xie H, Liu J, Alem Glison DM, Fleming JB (2021). “The clinical advances of proteolysis targeting chimeras in oncology”. Exploration of Targeted Anti-Tumor Therapy. 2 (6): 511–521. doi:10.37349/etat.2021.00061. PMC 9400722. PMID 36046114.
- Rathkopf DE, Patel MR, Choudhury AD, Rasco D, Lakhani N, Hawley JE, et al. (September 2024). “Safety and clinical activity of BMS-986365 (CC-94676), a dual androgen receptor ligand-directed degrader and antagonist, in heavily pretreated patients with metastatic castration-resistant prostate cancer”. Annals of Oncology. 36 (1): 76–88. doi:10.1016/j.annonc.2024.09.005. PMC 12094577. PMID 39293515.
| Clinical data | |
|---|---|
| Other names | BMS-986365; CC-94676 |
| Identifiers | |
| IUPAC name | |
| CAS Number | 2446929-86-6 |
| PubChem CID | 153513643 |
| ChemSpider | 133326102 |
| UNII | VA228VR2DI |
| KEGG | D12866 |
| ChEMBL | ChEMBL6068413 |
| Chemical and physical data | |
| Formula | C41H45F3N8O5S |
| Molar mass | 818.92 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
//////////gridegalutamide, ANAX, ADVECT, antiandrogen, antineoplastic, BMS 986365, CC 94676, BMS-986365, CC-94676, CEL 010355, VA228VR2DI,
Fanregratinib
Fanregratinib
CAS 1628537-44-9
MF C27H33ClN6O2, 509.0 g/mol
4-chloro-3-[2-[2-[4-[(3S,5R)-3,5-dimethylpiperazin-1-yl]anilino]pyrimidin-5-yl]ethyl]-5-methoxy-N-methylbenzamide
- 4-Chloro-3-(2-(2-((4-((3s,5r)-3,5-dimethylpiperazin-1-yl)phenyl)amino)pyrimidin-5-yl)ethyl)-5-methoxy-N-methylbenzamide
- 4-chloro-3-(2-(2-(4-((3S,5R)-3,5-dimethylpiperazin-1-yl)phenylamino)pyrimidin-5-yl)ethyl)-5-methoxy-N-methylbenzamide
- 4-chloro-3-[2-[2-[4-[(3S,5R)-3,5-dimethylpiperazin-1-yl]anilino]pyrimidin-5-yl]ethyl]-5-methoxy-N-methylbenzamide
- Benzamide, 4-chloro-3-[2-[2-[[4-[(3R,5S)-3,5-dimethyl-1-piperazinyl]phenyl]amino]-5-pyrimidinyl]ethyl]-5-methoxy-N-methyl-, cis-
- Benzamide, 4-chloro-3-[2-[2-[[4-[(3R,5S)-3,5-dimethyl-1-piperazinyl]phenyl]amino]-5-pyrimidinyl]ethyl]-5-methoxy-N-methyl-, rel-
- cis-4-Chloro-3-[2-[2-[[4-[(3R,5S)-3,5-dimethyl-1-piperazinyl]phenyl]amino]-5-pyrimidinyl]ethyl]-5-methoxy-N-methylbenzamide
- rel-4-Chloro-3-[2-[2-[[4-[(3R,5S)-3,5-dimethyl-1-piperazinyl]phenyl]amino]-5-pyrimidinyl]ethyl]-5-methoxy-N-methylbenzamide
fibroblast growth factor receptor tyrosine kinase inhibitor, antineoplastic, 8RWL2B2CLS
- OriginatorHutchison MediPharma
- DeveloperHutchison MediPharma; HUTCHMED
- ClassAntineoplastics; Small molecules
- Mechanism of ActionType 1 fibroblast growth factor receptor antagonists; Type 3 fibroblast growth factor receptor antagonists; Type-2 fibroblast growth factor receptor antagonists
- PreregistrationCholangiocarcinoma
- Phase IIMesothelioma
- Phase I/IISolid tumours
- 29 Dec 2025Preregistration for Cholangiocarcinoma (Late-stage disease, Metastatic disease, Second-line therapy or greater, Inoperable/Unresectable) in China (PO)
- 29 Dec 2025Updated efficacy data from a phase II trial in Cholangiocarcinoma released by HUTCHMED
- 03 Nov 2025HUTCHMED announces intention to submit new drug application to NMPA for Cholangiocarcinoma in first half of 2026
FANREGRATINIB is a small molecule drug with a maximum clinical trial phase of II and has 1 investigational indication.
Fanregratinib is a small molecule drug. The usage of the INN stem ‘-gratinib’ in the name indicates that Fanregratinib is a fibroblast growth factor receptor (FGFR) inhibitor. Fanregratinib has a monoisotopic molecular weight of 508.24 Da.
Fanregratinib is an orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) types 1, 2, and 3 (FGFR1/2/3), with potential antineoplastic activity. Upon administration, fanregratinib binds to and inhibits FGFR1/2/3, which may result in the inhibition of FGFR1/2/3-related signal transduction pathways. This inhibits proliferation in FGFR1/2/3-overexpressing tumor cells. FGFR, a family of receptor tyrosine kinases (RTKs) upregulated in many tumor cell types, plays a key role in cellular proliferation, migration and survival.
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=US159751913&_cid=P10-MKQ98D-55657-1
Example 9
Synthesis of Compounds 79-91, 146-155
Compound 79
4-chloro-3-(2-(2-((4-((3S,5R)-3,5-dimethylpiperazin-1-yl)phenyl)amino)pyrimidin-5-yl)ethyl)-5-methoxy-N-methylbenzamide
(C) 4-chloro-3-(2-(2-(4-((3S,5R)-3,5-dimethylpiperazin-1-yl)phenylamino)pyrimidin-5-yl)ethyl)-5-methoxy-N-methylbenzamide
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2014139465&_cid=P10-MKQ9F3-62190-1
Example 9: Synthesis of Compounds 78-103
Compound 78
4-chloro-3-(2-(2-((4-((3S,5/f)-3,5-dimethylpiperazin-l-yl)phenyl)amino)pyrimidin-5
-yl)ethyl)-5-methoxy-N-methylbenzamide
(A) Methyl 4-chloro-3-((JE)-2-(2-(4-((3S,5R)-3,5-dimethylpiperazin-l-yl)
phenylamino)pyrimidin-5-yl)vinyl)-5-methoxybenzoate
A mixture of (E)-methyl 4-chloro-3-(2-(2-chloropyrimidin-5-yl)vinyl)-5-methoxy benzoate (150mg, 0.442 mmol), 4-((35′,5i?)-3,5-dimethylpiperazin-l-yl)aniline (109 mg, 0.531 mmol) and TFA (0.1 mL, 1.326 mmol) in propan~2-oi (5 mL) was stirred at 150 °C for 1 h under microwave. The resulting mixture was concentrated, basified with ammonia water, purified via ISCO (DCM/MeOH) to afford the title compound as a
yellow solid (130 mg, 57.9% yield). MS (m/z): 508.2(M+H)+.
(B) 4-chloro-3-((£)-2-(2-(4-((3S,5R)-3,5-dimethylpiperazin-l-yl)phenylamino)pyrim idin-5-yl)vinyl)-5-methoxy-N-methylbenzamide
A mixture of methyl 4-chloro-3-((E)-2-(2-(4-((35′,5i?)-3,5-dimethylpiperazin-l-yl) phenylamino)pyrimidin-5-yl)vinyl)-5-methoxybenzoate (250 mg, 0.492 mmol) and methylamine (6 mL, 35% solution in ethanol) was stirred at 145 °C for 22 min under microwave. The resulting mixture was concentrated, purified via ISCO (DCM/MeOH) to afford the title compound as a yellow solid (145 mg, 58.1%> yield). MS (m/z):
506.9(M+H)+.
(C) 4-chloro-3-(2-(2-(4-((3S,5R)-3,5-dimethylpiperazin-l-yl)phenylamino)pyrimidin -5-yl)ethyl)-5-methoxy-N-methylbenzamide
A mixture of 4-chloro-3-((E)-2-(2-(4-((35*,5i?)-3,5-dimethylpiperazin-l-yl)
phenylamino)pyrimidin-5-yl)vinyl)-5-methoxy-N-methylbenzamide (120 mg, 0.237 mmol), 4-methylbenzenesulfonohydrazide (528 mg, 2.84 mmol) and sodium acetate (233 mg, 2.84 mmol) in THF (6mL) and water (6mL) was stirred overnight at 100 °C under nitrogen atmosphere. The resulting mixture was concentrated. The residue was partitioned between 2N HC1 (15 mL) and EA (15 mL). The aqueous layer was then adjusted to pH=8 with 30% NaOH and extracted with DCM (2* 15 mL). The combined extracts were concentrated and the residue was purified via ISCO (eluted with MeOH in H20 0-100%) to afford the title compound as a yellow solid (50 mg, 41.5% yield). MS (m/z): 509.0(M+H)+. 1H NM (400 MHz, CD3OD) δ 8.1 1 (s, 2H), 7.44 (d, J = 9.1 Hz, 2H), 7.37 (d, J = 2.0 Hz, 1H), 7.30 (d, J = 2.0 Hz, 1H), 6.95 (d, J = 9.1 Hz, 2H), 3.93 (s, 3H), 3.53 – 3.44 (m, 2H), 3.10 – 2.99 (m, 4H), 2.90 (s, 3H), 2.82 (t, J = 7.6 Hz, 2H), 2.25 (t, J = 7.5 Hz, 2H), 1.16 (d, J = 6.4 Hz, 6H).
PAT
- Novel pyrimidine and pyridine compounds and their usagePublication Number: WO-2014139465-A1Priority Date: 2013-03-15
- Novel pyrimidine and pyridine compounds and usage thereofPublication Number: WO-2014139145-A1Priority Date: 2013-03-15
- Pyrimidine and pyridine compounds and their usePublication Number: BR-112015020772-B1Priority Date: 2013-03-15
- Pyrimidine and pyridine compounds and their usagePublication Number: US-9701680-B2Priority Date: 2013-03-15Grant Date: 2017-07-11
- Novel pyrimidine and pyridine compounds and usage thereofPublication Number: US-2016052926-A1Priority Date: 2013-03-15
- Novel pyrimidine and pyridine compounds and their usagePublication Number: EP-2970120-A1Priority Date: 2013-03-15
- Novel pyrimidine and pyridine compounds and their usagePublication Number: EP-2970120-B1Priority Date: 2013-03-15Grant Date: 2018-09-12
- Novel pyrimidine and pyridine compounds and their usagePublication Number: US-2016024021-A1Priority Date: 2013-03-15
- The salts of a compound and the crystalline forms thereofPublication Number: WO-2021073494-A1Priority Date: 2019-10-14
- The salts of a compound and the crystalline forms thereofPublication Number: US-2023121346-A1Priority Date: 2019-10-14
- The salts of a compound and the crystalline forms thereofPublication Number: TW-202128669-APriority Date: 2019-10-14
- Salts of compounds and crystalline forms thereofPublication Number: CN-114555558-APriority Date: 2019-10-14
- SALTS OF THE COMPOUND 4-CHLORO-3-(2-(2-((4-((3S,5R)-3,5-DIMETHYLPIPERAZIN-1-YL)PHENYL)AMINO)PYRIMIDIN-5-YL)ETHYL)-5 -METHOXY-N-METHYLBENZAMIDE AND CRYSTALLINE FORMS THEREOFPublication Number: AR-120202-A1Priority Date: 2019-10-14
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
/////////fanregratinib, fibroblast growth factor receptor tyrosine kinase inhibitor, antineoplastic, 8RWL2B2CLS
New Drug Approvals 
