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SRT 1720



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SRT-1720 diHCl


CAS: 1001645-58-4 (di HCl) , 925434-55-5 (free base)   1001645-58-4 (HCl)
Chemical Formula: C25H25Cl2N7OS
Molecular Weight: 542.483
Elemental Analysis: C, 55.35; H, 4.65; Cl, 13.07; N, 18.07; O, 2.95; S, 5.91

SRT-1720 HCl, SRT-1720 hudrochloride; SRT1720; SRT-1720; SRT 1720; CAY10559; CAY-10559; CAY 10559; SIRT-1933; SIRT 1933; SIRT1933.

 N-(2-(3-(piperazin-1-ylmethyl)imidazo[2,1-b]thiazol-6-yl)phenyl)quinoxaline-2-carboxamide dihydrochloride


  • Molecular FormulaC25H23N7OS
  • Average mass469.561 Da

SRT-1720, also known as CAY10559 and is a drug developed by Sirtris Pharmaceuticals intended as a small-molecule activator of the sirtuin subtype SIRT1. It has similar activity in the body to the known SIRT1 activator resveratrol, but is 1000x more potent. In animal studies it was found to improve insulin sensitivity and lower plasma glucose levels in fat, muscle and liver tissue, and increased mitochondrial and metabolic function. A study of SRT1720 conducted by the National Institute on Aging found that the drug may extend the lifespan of obese mice by 44% .

SRT1720 is an experimental drug that was studied by Sirtris Pharmaceuticals intended as a small-molecule activator of the sirtuinsubtype SIRT1. The compound has been studied in animals, but safety and efficacy in humans have not been established.

Animal research

In animal models of obesity and diabetes SRT1720 was found to improve insulin sensitivity and lower plasma glucose levels in fat, muscle and liver tissue, and increase mitochondrial and metabolic function.[1] In mice rendered obese and diabetic by feeding a high-fat, high-sugar diet, a study performed at the National Institute of Aging found that feeding chow infused with the highest dose of SRT1720 beginning at one year of age increased mean lifespan by 18%, and maximum lifespan by 5%, as compared to other short-lived obese, diabetic mice; however, treated animals still lived substantially shorter lives than normal-weight mice fed normal chow with no drug.[2] In a later study, SRT1720 increased mean lifespan of obese, diabetic mice by 21.7%, similar to the earlier study, but there was no effect on maximum lifespan in this study.[3] In normal-weight mice fed a standard rodent diet, SRT1720 increased mean lifespan by just 8.8%, and again had no effect on maximum lifespan.[3]

Since the discovery of SRT1720, the claim that this compound is a SIRT1 activator has been questioned[4][5][6] and further defended.[7][8]

Although SRT1720 is not currently undergoing clinical development, a related compound, SRT2104, is currently in clinical development for metabolic diseases.[9]


Letters in Drug Design & Discovery, 10(9), 793-797; 2013

The Identification of the SIRT1 Activator SRT2104 as a Clinical Candidate

Author(s): Pui Yee Ng, Jean E. Bemis, Jeremy S. Disch, Chi B. Vu, Christopher J. Oalmann, Amy V. Lynch,David P. Carney, Thomas V. Riera, Jeffrey Song, Jesse J. Smith, Siva Lavu, Angela Tornblom, Meghan Duncan, Marie Yeager, Kristina Kriksciukaite, Akanksha Gupta, Vipin Suri, Peter J. Elliot, Jill C. Milne, Joseph J. Nunes, Michael R. Jirousek, George P. Vlasuk, James L. Ellis, Robert B. Perni.

Journal Name: Letters in Drug Design & Discovery

Volume 10 , Issue 9 , 2013


Milne, J.C.; Lambert, P.D.; Schenk, S.; Carney, D.P.; Smith, J.J.; Gagne, D.J.; Jin, L.; Boss, O.; Perni, R.B.; Vu, C.B.; Bemis, J.E.; Xie, R.; Disch, J.S.; Ng, P.Y.; Nunes, J.J.; Lynch, A.V.; Yang, H.; Galonek, H.; Israelian, K.; Choy, W.; Iffland, A.; Lavu, S.; Medvedik, O.; Sinclair, D.A.; Olefsky, J.M.; Jirousek, M.R.; Elliott, P.J.; Westphal, C.H.
Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
Nature 2007, 450(7170): 712


WO 2007019417

WO 2007019416

WO 2007019345

WO 2007019344

WO 2007019346

WO 2008115518


Vu, Chi B.; Journal of Medicinal Chemistry 2009, VOL 52(5), PG 1275-1283

Abstract Image

A series of imidazo[1,2-b]thiazole derivatives is shown to activate the NAD+-dependent deacetylase SIRT1, a potential new therapeutic target to treat various metabolic disorders. This series of compounds was derived from a high throughput screening hit bearing an oxazolopyridine core. Water-solubilizing groups could be installed conveniently at either the C-2 or C-3 position of the imidazo[1,2-b]thiazole ring. The SIRT1 enzyme activity could be adjusted by modifying the amide portion of these imidazo[1,2-b]thiazole derivatives. The most potent analogue within this series, namely, compound 29, has demonstrated oral antidiabetic activity in the ob/ob mouse model, the diet-induced obesity (DIO) mouse model, and the Zucker fa/fa rat model.

Discovery of Imidazo[1,2-b]thiazole Derivatives as Novel SIRT1 Activators

Sirtris Pharmaceuticals, 200 Technology Square, Cambridge, Massachusetts 02139
J. Med. Chem.200952 (5), pp 1275–1283
DOI: 10.1021/jm8012954

* To whom correspondence should be addressed. Phone: (617)-252-6920, extension 2129. Fax: (617)-252-6924. E-mail:, †

Present address: Department of Medicine, Division of Endocrinology and Metabolism, University of California—San Diego, 9500 Gilman Drive, La Jolla, CA 92093.

Preparation of N-(2-(3-(Piperazin-1-ylmethyl)imidazo[2,1-b]thiazol-6-yl)phenyl)quinoxaline-2-carboxamide (29)

Essentially the same procedure as detailed in the preparation of 3,4,5-trimethoxy-N-(2-(3-(piperazin-1-ylmethyl)imidazo[2,1-b]thiazol-6-yl)phenyl)benzamide was employed except that 2-quinoxaloyl chloride was used.
Mp: dec (HCl salt), 221.4 °C (freebase).
 1H NMR (300 MHz, DMSO-d6) δ 9.60 (br s, 1 H), 8.88 (d, 1 H, J = 8 Hz), 8.60 (br s, 1 H), 8.50 (s, 1 H), 8.0−8.30 (m, 5 H), 7.78 (d, 1 H, J = 8 Hz), 7.10−7.33 (m, 4 H), 3.90 (br s, 2 H), 3.00−3.10 (m, 4H), 2.60−2.80 (m, 4 H).
13C NMR (100 MHz, DMSO-d6): δ 47.49, 49.88, 111.45, 120.47, 121.84, 124.02, 127.04, 128.10, 129.20, 129.23, 131.39, 132.15, 135.39, 139.54, 143.03, 143.80, 144.36, 144.62, 147.76, 161.57.
High resolution MS, calcd for C25H23N7OS [M + H]+ 470.1763; found, 470.1753.


  1. ^ Milne JC; Lambert PD; Schenk S; Carney DP; Smith JJ; Gagne DJ; Jin L; Boss O; Perni RB; Vu CB; Bemis JE; Xie R; Disch JS; Ng PY; Nunes JJ; Lynch AV; Yang H; Galonek H; Israelian K; Choy W; Iffland A; Lavu S; Medvedik O; Sinclair DA; Olefsky JM; Jirousek MR; Elliott PJ; Westphal CH (November 2007). “Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes”Nature450(7170): 712–6. doi:10.1038/nature06261PMC 2753457PMID 18046409.
  2. ^ Minor RK; Baur JA; Gomes AP; Ward TM; Csiszar A; Mercken EM; Abdelmohsen K; Shin YK; Canto C; Scheibye-Knudsen M; Krawczyk M; Irusta PM; Martín-Montalvo A; Hubbard BP; Zhang Y; Lehrmann E; White AA; Price NL; Swindell WR; Pearson KJ; Becker KG; Bohr VA; Gorospe M; Egan JM; Talan MI; Auwerx J; Westphal CH; Ellis JL; Ungvari Z; Vlasuk GP; Elliott PJ; Sinclair DA; de Cabo R (Aug 2011). “SRT1720 improves survival and healthspan of obese mice”Scientific Reports1 (70): 70. doi:10.1038/srep00070PMC 3216557PMID 22355589. Retrieved 1 March 2014.
  3. Jump up to:a b Mitchell SJ; Martin-Montalvo A; Mercken EM; et al. (Feb 2014). “The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet”Cell Reports6 (4): 836–43. doi:10.1016/j.celrep.2014.01.031PMC 4010117PMID 24582957. Retrieved 1 March 2014.
  4. ^ Pacholec M; Chrunyk BA; Cunningham D; Flynn D; Griffith DA; Griffor M; Loulakis P; Pabst B; Qiu X; Stockman B; Thanabal V; Varghese A; Ward J; Withka J; Ahn K (January 2010). “SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1”J Biol Chem285 (11): 8340–8351. doi:10.1074/jbc.M109.088682PMC 2832984PMID 20061378.
  5. ^ Beher D; Wu J; Cumine S; Kim KW; Lu SC; Atangan L; Wang M (December 2009). “Resveratrol is not a direct activator of SIRT1 enzyme activity”. Chem Biol Drug Des74 (6): 619–24. doi:10.1111/j.1747-0285.2009.00901.xPMID 19843076.
  6. ^ Zarse, K.; Schmeisser, S.; Birringer, M.; Falk, E.; Schmoll, D.; Ristow, M. (2010). “Differential Effects of Resveratrol and SRT1720 on Lifespan of AdultCaenorhabditis elegans”. Hormone and Metabolic Research42 (12): 837–839. doi:10.1055/s-0030-1265225PMID 20925017.
  7. ^ Callaway E (2010-08-16). “GlaxoSmithKline strikes back over anti-ageing pills: Drugs do work as thought, says pharmaceutical giant”Naturedoi:10.1038/news.2010.412.
  8. ^ Dai H; Kustigian L; Carney D; Case A; Considine T; Hubbard BP; Perni RB; Riera TV; Szczepankiewicz B; Vlasuk GP; Stein RL (August 2010). “SIRT1 activation by small molecules – kinetic and biophysical evidence for direct interaction of enzyme and activator”J Biol Chem285 (43): 32695–32703. doi:10.1074/jbc.M110.133892PMC 2963390PMID 20702418.
  9. ^ “Sirtuin Pipeline”Sirtris Pharmaceuticals.
PubChem CID
CompTox Dashboard(EPA)
Chemical and physical data
Formula C25H23N7OS
Molar mass 469.560 g/mol g·mol−1
3D model (JSmol)

////////////SRT-1720 DI HCl, obesity, diabetes, SRT 1720,  Sirtris Pharmaceuticals,  CAY10559,  CAY 10559, Preclinical


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DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA, ROW2TECH, NIPER-G, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India as ADVISOR, earlier assignment was with GLENMARK LIFE SCIENCES LTD, as CONSUlTANT, Retired from GLENMARK in Jan2022 Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 32 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 32 PLUS year tenure till date Feb 2023, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 100 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 100 Lakh plus views on dozen plus blogs, 227 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 38 lakh plus views on New Drug Approvals Blog in 227 countries...... , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc He has total of 32 International and Indian awards

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