Home » Preclinical drugs (Page 12)
Category Archives: Preclinical drugs
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 |
Novel Drug Shows Promise for Early Stage Breast Cancer
pertuzumab
TUESDAY Sept. 10, 2013 — A drug already used to treat advanced breast cancer also appears to shrink early stage breast tumors, potentially offering women a first-of-its-kind treatment option, U.S. health regulators say.
read all at
http://www.drugs.com/news/novel-shows-promise-early-stage-breast-cancer-47311.html
Biotie Announces Start of Clinical Study With Nepicastat (SYN117) in Cocaine Dependence
NEPICASTAT
TURKU, FINLAND–BIOTIE THERAPIES CORP. STOCK EXCHANGE RELEASE 10 May 2013 at 9.00 a.m.
Biotie announces start of clinical study with nepicastat (SYN117) in cocaine dependence
Biotie Therapies today announced the start of a Phase 2 clinical study evaluating nepicastat (SYN117) in cocaine dependence. The National Institute on Drug Abuse (NIDA) at the US National Institutes of Health is funding the conduct of the study under a Collaborative Research and Development Agreement (CRADA) signed in December 2011.
The study is a randomized, double-blind placebo-controlled 11-week trial and is expected to enroll about 180 treatment-seeking cocaine-dependent subjects. The study will be conducted at approximately 12 US clinics specializing in the treatment of drug dependence.
The trial is expected to take approximately two years to complete.
ABOUT NEPICASTAT (SYN117)
Nepicastat is an orally administered, potent and selective inhibitor of the enzyme dopamine beta-hydroxylase (DBH) which converts dopamine into norepinephrine. Like many other addictions, cocaine dependence is driven by dysregulation in the dopamine-reward system. Inhibition of DBH by nepicastat increases levels of dopamine, which may reduce craving for cocaine, and reduces the levels of norepinephrine, which may decrease the pleasurable responses to cocaine and the potential for stress-induced relapse following withdrawal. Biotie has previously conducted a placebo-controlled Phase 2a study in non-treatment seeking cocaine addicts. The study showed that nepicastat had a favourable safety profile and was well tolerated when administered with cocaine.
Nepicastat has also been evaluated as a potential treatment for post-traumatic stress disorder (PTSD). In December 2012, Biotie announced top-line data from an investigator-initiated Phase 2 study in PTSD. In this study, nepicastat was generally well tolerated but was not effective in relieving PTSD-associated symptoms when compared to placebo. Biotie is evaluating data from this study in further detail and will then decide on next steps with nepicastat in PTSD
Biotie holds full rights to nepicastat and will be able to use data from studies conducted with NIDA to support future potential regulatory submissions.
ABOUT BIOTIE
Biotie is a specialized drug development company focused on the development of drugs for neurodegenerative and psychiatric disorders (e.g. Parkinson’s disease, Alzheimer’s disease and other cognitive disorders, alcohol and drug dependence (addiction) and post-traumatic stress disorder), and inflammatory and fibrotic liver disease. The company has a strong and balanced development portfolio with several innovative small molecule and biological drug candidates at different stages of clinical development. Biotie’s products address diseases with high unmet medical need and significant market potential.
Biotie’s most advanced product, Selincro (nalmefene), licensed to H. Lundbeck A/S, has on 28 February 2013 received European marketing authorization for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high level of alcohol consumption. In addition, Biotie has a strategic collaboration with UCB Pharma S.A. covering tozadenant which is transitioning into Phase 3 development for Parkinson’s disease. Biotie shares are listed on NASDAQ OMX Helsinki Ltd.
Nepicastat (INN, codenamed SYN117, RS-25560-197) is an inhibitor of dopamine beta-hydroxylase, an enzyme that catalyzes the conversion of dopamine to norepinephrine.[1]
It has been studied as a possible treatment for congestive heart failure, and appears to be well tolerated as such.[2] As of 2012, clinical trials to assess nepicastat as a treatment forpost-traumatic stress disorder (PTSD) and cocaine dependence have been completed.[3][4]
Synthesis
- Stanley WC, Li B, Bonhaus DW, et al. (August 1997). “Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel, potent and selective inhibitor of dopamine-beta-hydroxylase”. Br J Pharmacol 121 (8): 1803–9. doi:10.1038/sj.bjp.0701315.PMC 1564872. PMID 9283721.
- Hegde SS, Friday KF (December 1998). “Dopamine-beta-hydroxylase inhibition: a novel sympatho-modulatory approach for the treatment of congestive heart failure”. Current pharmaceutical design 4 (6): 469–79. PMID 10197057.
- “Pharmacogenetic Clinical Trial of Nepicastat for Post Traumatic Stress Disorder (PTSD)”. ClinicalTrials.gov. U.S. National Institutes of Health. June 4, 2008. Retrieved on February 1, 2012.
- “Study of Safety and Potential Efficacy of SYN117 in Cocaine Dependent Volunteers”. ClinicalTrials.gov. U.S. National Institutes of Health. August 15, 2008. Retrieved on February 1, 2012.
Paragazole Excels as Breast Cancer Treatment
New combination therapy cures patient with advanced ovarian cancer
A novel ovarian cancer treatment made from tumour cells has cured a woman in the US with an advanced form of the disease, scientists at the Perelman School of Medicine at the University of Pennsylvania have announced.
During a preliminary trial of the two-step immunotherapy, the patient achieved complete remission, while seven other women had no measurable disease at the end of the study.
The therapy includes a personalised immune cell vaccination made from the patients’ live tumour cells and adoptive T-cell therapy.
Both treatments are given in conjunction with Avastin (bevacizumab), a drug developed by Roche that controls the blood vessel growth that feeds tumours.
The second step in the study involved the isolation of immune cells, known as dendritic cells, from the patients’ blood through a process called apheresis, similar to the process used for blood donation.
Announcing its findings at the American Association of Cancer Research (AACR) Annual Meeting in Washington DC on Saturday, the research team reported that in the study of 31 patients, vaccination therapy alone showed a 61% clinical benefit, and the combination of both therapies benefited around 75% of participants.
Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the US, taking the lives of 14,000 people each year.
Lead author of the study Lana Kandalaft said; “Given these grim outcomes, there is definitely a vast unmet need for the development of novel, alternate therapies.”
“This is the first time such a combination immunotherapy approach has been used for patients with ovarian cancer, and we believe the results are leading us toward a completely new way to treat this disease.”
The vaccine trial is still open to accrual to test new combinatorial strategies.
ELQ-300, Promising new antimalarial to enter clinical testing phase
ELQ-300
6-chloro-7-methoxy-2-methyl-3-{4-[4-(trifluoromethoxy)phenoxy]phenyl}quinolin-4(1H)-one
21 MAR 2013
A promising new antimalarial drug with the potential to cure and block transmission of the mosquito-borne disease has been discovered by researchers.
The drug, known as ELQ-300, has demonstrated preventative transmission-blocking and a low likelihood of developing rapid resistance to major strains of malaria parasites.
Researchers say it is also likely that the drug could be produced more cheaply than existing antimalarials.
ELQ-300 is now moving into clinical testing.
This new treatment was developed by the Medicines for Malaria Venture (MMV) drug discovery initiative, which is made up of researchers from Oregon Health & Science University in Portland, Drexel University in Philadelphia, University of South Florida and Monash University in Australia.
The full details of their research was published yesterday in the Science Translational Medicine journal.
During the process of creating the drug, researchers discovered and developed a series of potent compounds to combat malaria quinolones.
From this series, they narrowed down the most effective drug candidates to one lead drug, ELQ-300.
“This is one of the first drugs ever to kill the malaria parasite in all three stages of its life cycle,” said Dr Kyle, a member of the Global Infectious Diseases Research team at the USF College of Public Health.
“So, it may become part of a new-generation therapy that not only treats sick people and prevents them from getting ill, but also blocks the transmission of malaria from mosquitoes to humans … If the drug can break the parasite life cycle, we may ultimately eradicate the disease.”
Malaria is a tropical disease that kills nearly one million people a year, mostly in developing countries.
ELQ-300 was derived from the first antimalarial quinolone, endochin, discovered more than 60 years ago but never pursued as a treatment because it appeared not to work in humans.
Researchers used new technology to develop this latest class of drug.
“This was a very challenging project requiring years of hard work, collaboration across disciplines, and a good portion of luck,” said Dr. Manetsch, from the University of South Florida.
ELQ-300 is an experimental antimalarial medication. It is an endochin-like quinolone and the first in a new class of antimalarials known as quinolone-3-diarylethers.[1]
ELQ-300 acts as an inhibitor of the mitochondrial cytochrome bc1 complex (complex III in the electron transport chain).[1] In preclinical studies with mice, it was found to be highly active against Plasmodium falciparum and Plasmodium vivax at all life cycle stages that play a role in the transmission of malaria, and to have good oral bioavailability.[1]
- Nilsen A et al (2013). “Quinolone-3-diarylethers: a new class of antimalarial drug”.Science Translational Medicine 5 (177): 177ra37. doi:10.1126/scitranslmed.3005029.ISSN 1946-6234.
- “NIH-Supported Researchers Identify New Class of Malaria Compounds” (Press release). U.S. National Institutes of Health. March 20, 2013.
- A Nilsen et al, Sci. Transl. Med., 2013, DOI:10.1126/scitranslmed.3005029
- ‘ELQ-300 targets the parasite mitochondrion,’ Riscoe says. In most organisms, the primary function of the mitochondria is to produce energy by making adenosine triphosphate (ATP). ‘But in the parasite, the primary function is to produce the pyrimidine building blocks for DNA [thymine and cytosine].’ The molecule prevents the synthesis of those bases, which prevents the parasite from reproducing, so it dies.
Hyaluronan initiates chondrogenesis mainly via CD44 in human adipose derived stem cells.
Source
1Kaohsiung Medical University.
Abstract
Cell-matrix adhesion is one of the important interactions that regulate stem cell survival, self-renewal, and differentiation. Our previous report indicated that a microenvironment enriched with hyaluronan (HA) initiated and enhanced chondrogenesis in human adipose derived stem cells (hADSCs). We further hypothesize that HA-induced chondrogenesis in hADSCs is mainly due to the interaction of HA and CD44 (HA-CD44), a cell surface receptor of HA. The HA-CD44 interaction was tested by examining the mRNA expression of hyaluronidase-1 (Hyal-1) and chondrogenic marker genes (SOX-9, collagen type II, and aggrecan) in hADSCs cultured on HA-coated wells. Cartilaginous matrix formation, sulfated glycosaminoglycan (sGAG) and collagen productions by hADSCs affected by HA-CD44 interaction were tested in a 3D fibrin hydrogel. About 99.9% of hADSCs possess CD44. The mRNA expressions of Hyal-1 and chondrogenic marker genes were up-regulated by HA in hADSCs on HA-coated wells. Blocking HA-CD44 interaction by anti-CD44 antibody completely inhibited Hyal-1 expression and reduced chondrogenic marker gene expression, which indicates that HA induced chondrogenesis in hADSCs mainly acts through HA-CD44 interaction. A two-hour pre-incubation and co-culture of cells with HA in hydrogel (HA/fibrin hydrogel) not only assisted in hADSC survival but also enhanced expression of Hyal-1 and chondrogenic marker genes. Higher levels of sGAG and total collagen were also found in HA/fibrin hydrogel group. Immunocytochemistry showed more collagen type II but less collagen type X in HA/fibrin than in fibrin hydrogels. Our results indicate that signaling triggered by HA-CD44 interaction significantly contributes to HA-induced chondrogenesis and may be applied to ADSC-based cartilage regeneration.
Hyaluronan (also called hyaluronic acid or hyaluronate or HA) is an anionic,nonsulfated glycosaminoglycan distributed widely throughout connective,epithelial, and neural tissues. It is unique among glycosaminoglycans in that it is nonsulfated, forms in the plasma membrane instead of the Golgi, and can be very large, with its molecular weight often reaching the millions.[2] One of the chief components of the extracellular matrix, hyaluronan contributes significantly to cell proliferation and migration, and may also be involved in the progression of some malignant tumors.
The average 70 kg (154 lbs) person has roughly 15 grams of hyaluronan in the body, one-third of which is turned over (degraded and synthesized) every day.[3]Hyaluronic acid is also a component of the group A streptococcal extracellularcapsule,[4] and is believed to play a role in virulence.[5][6]
- Hyaluronate Sodium in the ChemIDplus database, consulté le 12 février 2009
- Frasher, J.R.E et al’; Laurent, T. C.; Laurent, U. B. G. (1997).“Hyaluronan: its nature, distribution, functions and turnover”(PDF). Journal of Internal Medicine 242 (1): 27–33.doi:10.1046/j.1365-2796.1997.00170.x. PMID 9260563. Retrieved 2009-06-05.
- Stern R (August 2004). “Hyaluronan catabolism: a new metabolic pathway”. Eur J Cell Biol 83 (7): 317–25.doi:10.1078/0171-9335-00392. PMID 15503855.
- Sugahara, K.; N.B. Schwartz and A. Dorfman (1979).“Biosynthesis of hyaluronic acid by Streptococcus“. Journal of Biological Chemistry 254 (14): 6252–6261. PMID 376529.
- Wessels, M.R.; A.E. Moses, J.B. Goldberg and T.J. DiCesare (1991). “Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci”. PNAS 88 (19): 8317–8321.doi:10.1073/pnas.88.19.8317. PMC 52499.PMID 1656437.
- Schrager, H.M.; J.G. Rheinwald and M.R. Wessels (1996).“Hyaluronic acid capsule and the role of streptococcal entry into keratinocytes in invasive skin infection”. Journal of Clinical Investigation 98 (9): 1954–1958. doi:10.1172/JCI118998.PMC 507637. PMID 8903312.
Hyaluronic Acid
HSP70i, A genetically modified protein, on Experimental Vitiligo Treatment, Shows Promise in Mice
WEDNESDAY Feb. 27, 2013 — A genetically modified protein could provide the first effective treatment for the skin condition vitiligo, a new study in mice suggests.
People with vitiligo have white patches on the face, hands and other parts of the body. Vitiligo is an autoimmune disorder in which the immune system becomes overactive and kills the pigment cells that give skin its color.
Researchers at the Loyola University Chicago Stritch School of Medicine developed a genetically modified protein that reversed vitiligo in mice and had similar effects on human skin tissue samples. Findings from animal studies do not always hold up in human trials, however.
A protein called HSP70i plays a major role in the autoimmune response that causes vitiligo. The researchers genetically modified an amino acid in the protein in order to create a mutant version of HSP70i. This version replaces normal HSP70i and reverses the autoimmune response that causes vitiligo, the study authors explained in a Loyola news release.
When the mutant HSP70i was given to mice with vitiligo, their salt-and-pepper fur turned black, giving them a normal appearance. The mutant protein had a similar effect on human skin samples, according to the study, published in the current issue of the journal Science Translational Medicine.
Researcher I. Caroline Le Poole, a professor in Loyola’s Oncology Institute, and colleagues are seeking approval and funding to conduct a clinical trial of the modified protein in humans.
About 1 million Americans have vitiligo, which affects about one in 200 people worldwide. There are no long-term effective treatments for the condition. Current options include steroid creams, light therapy and skin grafts, but none of them can prevent vitiligo from progressing.
More information
The U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases has more about vitiligo.
UC Riverside’s Michael Pirrung announces development of TIR-199 for renal (kidney) cancer at conference in Dubai
The compound TIR-199 that holds much promise in the laboratory in fighting renal (kidney) cancer. feb19,2013
RIVERSIDE, Calif. — Chemists at the University of California, Riverside have developed a compound that holds much promise in the laboratory in fighting renal (kidney) cancer.
Named TIR-199, the compound targets the “proteasome,” a cellular complex in kidney cancer cells, similar to the way the drug bortezomib, approved by the Food and Drug Administration, targets and inhibits the proteasome in multiple myeloma cells, a cancer coming from bone marrow.
Michael Pirrung, a distinguished professor of chemistry at UC Riverside, announced the development of TIR-199 in a lecture he gave on Feb. 19 at the 5th International Conference on Drug Discovery and Therapy, held in Dubai, UAE.
Operating like the garbage dump of a cell, the proteasome breaks down proteins. Drugs that block the action of proteasomes are called proteasome inhibitors, and have been shown to have activity against a variety of cancer cell lines, albeit with mixed results. For example, bortezomib, though effective against multiple myeloma, has many side effects because cells other than bone marrow cells are affected.
“The novel feature of our new proteasome inhibitor, TIR-199, is that it is nearly as potent as bortezomib, but is selective in inhibiting the growth of only renal cancer cell lines,” Pirrung said. “It’s what makes TIR-199 attractive.”
The TIR-199 research project at UC Riverside began about four years ago after a multidisciplinary, international team reported on a class of compounds that act on the proteasome. These compounds are the “syringolin” natural products — such as a compound produced naturally by the wheat-infecting bacterium Pseudomonas syringae. TIR-199 is a synthetic relative of syringolin.
Michael Pirrung is a distinguished professor of chemistry at UC Riverside. Photo credit: I. Pittalwala, UC Riverside.
Structure of Syringolin A.
The ring structure of syringolin A is formed by the two nonproteinogenic amino acids 5-methyl-4-amino-2-hexenoic acid and 3,4-dehydrolysine. The α-amino group of the latter is joined by a peptide bond to a valine residue, which is linked to another valine residue via a urea moiety.
FDA approves UCLA IND application to commence embryonic stem cell-based trial
12 feb 2013
The USFDA has approved the investigator investigational new drug (IND) application of University of California, Los Angeles (UCLA), the clinical partner of Advanced Cell Technology (ACT), to commence a clinical trial using the human embryonic stem cells (hESCs)-derived cells to treat severe myopia.
Embryonic stem cell-based trial was designed to assess the hESC-derived ACT’s retinal pigment epithelial (RPE) cells in patients with severe myopia (nearsightedness).
ACT chairman and CEO Gary Rabin said, “We are pleased to be on track to broaden the scope of our RPE program with the initiation of the new Investigator IND.”
Human embryonic stem cells (hESCs) are pluripotent cells derived from the inner cell mass of the blastocyst. They have the ability to renew themselves and to differentiate into a variety of different cell types that are found in the body. Unlike somatic or ‘adult’ stem cells, hESCs proliferate indefinitely. This, together with their ability to differentiate into most adult cell types, has resulted in the preferred use of these cells for research and therapeutic applications, as they represent a potentially indefinite source of therapeutic cells. Any cell therapy derived from hESCs would be allogeneic by nature. Some current studies involve the potential therapeutic application of hESCs for spinal cord injury, age-related macular degeneration (AMD), cardiovascular diseases, and diabetes. Among the start up cell therapy companies, Geron and Advanced Cell Technologies have pioneered clinical trials using cells differentiated from hESCs.
New Drug Approvals 