Navigation Links
Prolexys Pharmaceuticals and Columbia University Researchers,Publish Study on Anti-Tumor Properties of a Selective Small,Molecule Anti-Tumor Agent With Novel Mechanism of Action

SALT LAKE CITY, June 14, 2007 /PRNewswire/ -- Prolexys Pharmaceuticals and announced today a publication describing the properties of the selective small molecule anti-tumor agent, erastin. Prolexys and Columbia applied the company's chemi-proteomics technology to understand the mechanism of action of erastin. The results, to be published in the June 14, 2007 issue of the journal Nature reveal that erastin binds to mitochondrial voltage- dependent anion channels (VDACs) -- a novel target for anti-cancer drugs. Knock-down of VDAC2 and VDAC3 gene expression causes resistance to erastin, implicating the involvement of these two proteins in erastin-mediated cell death. Treatment of cells with erastin results in VDAC-protein-mediated mitochondrial dysfunction, release of oxidative species and, ultimately, cell death. This process has a degree of selectivity for cells with aberrantly active RAS pathway. In normal cells, RAS pathway is involved in growth and differentiation of cells; however the aberrant activation of this pathway results in uncontrolled tumor growth.

Dr. Brent Stockwell, currently an Associate Professor of Biological Sciences and of Chemistry at , identified erastin as a small molecule anti-cancer agent that exhibits lethality in human tumor cells with mutations in RAS-related cancer genes such as HRAS, KRAS or BRAF, beginning when he was a Fellow at the Whitehead Institute for Biomedical Research. In February 2005, Prolexys signed an exclusive licensing agreement with the Massachusetts Institute of Technology, as the licensing agent of , and the Whitehead Institute, which provides Prolexys with exclusive, worldwide rights to a patent estate covering selective anti-tumor compounds in the erastin family. "This paper demonstrates that it is feasible to discover compounds that produce cancer-cell-selective toxicity and to use these to understand cell death mechanisms in cancer cells; furthermore, the approach revealed a novel cell death pathway," said Dr. Stockwell.

Prolexys launched a medicinal chemistry effort in 2005 to create small molecule analogs of erastin with improved pharmaceutical properties. This effort resulted in the identification of a close structural analog, PRLX 93936, which shows improvement in potency, solubility, and in vivo activity, compared to erastin. PRLX 93936 shows robust and selective toxicity in a wide variety of tumor cell-lines, and causes complete tumor regression in mouse xenograft models of fibrosarcoma, pancreatic cancer, ovarian cancer, colon cancer, and melanoma. Prolexys plans to file an Investigational New Drug (IND) Application for PRLX 93936 with the U.S. Food and Drug Administration (FDA) in June, 2007. Although PRLX 93936 was created as a result of screening hundreds of erastin-related small molecules, its molecular mechanism of action may differ from those of erastin. "Prolexys and collaborators continue to work towards understanding the molecular basis of the unique tumor-selective mechanism of action of erastin and PRLX 93936," said Dr. Sudhir Sahasrabudhe, Chief Scientific Officer of Prolexys Pharmaceuticals.

"The approach described in this paper is a powerful way to identify and test small molecule therapeutics and translate them into the clinic in a time- efficient and cost-efficient manner. We are very excited about evaluating the therapeutic potential of molecules with novel mechanisms of action, such as PRLX 93936 in patients with pancreatic cancer and other solid tumors," said Dr. Daniel Von Hoff, Principal clinical investigator of PRLX 93936, and TGen's Physician-in-Chief and Director of TGen's Clinical Research Service in Scottsdale, Arizona

About Prolexys Pharmaceuticals: Prolexys Pharmaceuticals, Inc. is a privately held biopharmaceutical company focused on discovering small molecule drugs that act on novel therapeutic targets. The Company's therapeutic focus is in cancer and res piratory disease indications where Prolexys has identified novel therapeutic targets and small molecule compounds active at these targets. Prolexys' ability to identify and validate novel targets is driven by its technological leadership in the field of proteomics and the application of proteomics technologies to its own, and its partners, drug discovery programs. For more information about Prolexys, visit the company's website at

About Columbia University: A leading academic and research university, Columbia continually seeks to advance the frontiers of knowledge and to foster a campus community deeply engaged in understanding and addressing the complex global issues of our time. Columbia's extensive public service initiatives, cultural collaborations and community partnerships help define the University's underlying values and mission to educate students to be both leading scholars and informed, engaged citizens. Founded in 1754 as King's College, in the City of New York is the country's fifth oldest institution of higher learning.

CONTACT: Dr. Sudhir Sahasrabudhe, CSO of Prolexys Pharmaceuticals,+1-801-303-1714

Web site:

Terms and conditions of use apply
Copyright © 2007 PR Newswire Association LLC. All rights reserved.
A United Business Media Company


Related medicine technology :

1. BioSante Pharmaceuticals Announces New Findings for Potential Bird Flu Vaccine
2. Portola Pharmaceuticals Announces Positive Data from a Phase II Study of its Factor Xa Inhibitor at the XXI Congress of the International Society on Thrombosis and Haemostasis
3. Manhattan Pharmaceuticals Announces Results of Phase 2a Studies for Oral Oleoyl-estrone
4. Auxilium Pharmaceuticals to Present at the 2007 CEUT Emerging Growth Opportunities Conference
5. Sunesis Pharmaceuticals to Present at the C. E. Unterberg, Towbin Emerging Growth Conference
6. EPIX Pharmaceuticals to Present at the C.E. Unterberg, Towbin Emerging Growth Opportunities Conference
7. Pro-Pharmaceuticals Updates Progress of Clinical Trials & Davanat 505 (b)(2) Filings
8. Cosmo Pharmaceuticals Reports Positive Preliminary Phase II/III Data with Rifamycin MMX in Infectious Diarrhea
9. Portola Pharmaceuticals Announces Positive Phase II EXPERT Results and Additional Oral and Poster Presentations at the XXI Congress of the International Society on Thrombosis and Haemostasis (ISTH)
10. Cyclacel Pharmaceuticals Announces Results of Phase II Seliciclib Combination Studies
11. Arisaph Pharmaceuticals Announces Results of its Potent Smart DPP-4 Inhibitor, ARI-2243, at the ADA
Post Your Comments:
(Date:11/30/2015)... 2015   Royal Philips  (NYSE: PHG ... Radiology Solutions, a fully integrated, consultative approach to ... data-driven practice management approaches that combine imaging systems, ... improve care delivery and reduce costs. Making its ... North America Annual Meeting (RSNA) in ...
(Date:11/30/2015)... -- global cell culture market is expected to ... by 2022 at a CAGR of 7.1% therein. --> ... 2013 value of US$6.1 bn to US$11.3 bn by 2022 at ... has announced the release of a new market research study, detailing ... Culture Market - Global Industry Analysis, Size, Share, Growth, Trends and ...
(Date:11/30/2015)... , Nov. 30, 2015   Royal Philips ... Implant, the industry,s first MRI guided user interface and ... of patients with MR Conditional implants, such as knee ... 2015 Radiological Society of North America Annual Meeting ... and supports diagnostic confidence of this growing patient population. ...
Breaking Medicine Technology:
(Date:11/30/2015)... ... 30, 2015 , ... Until now, the St. Louis Fetal Care Institute ... of Myelomeningocele Study) trial. One of these exclusion criteria was a BMI above 34.9. ... to 24.9 is considered normal, 25 - 29.9 is overweight and above 30 is ...
(Date:11/30/2015)... ... November 30, 2015 , ... Thermi™, a world ... announce that its ThermiRFR temperature controlled radiofrequency platform has received CE marking and ... platform which uses temperature as a clinical endpoint. The technology has been ...
(Date:11/30/2015)... ... November 30, 2015 , ... The world of hair transplants and restoration is ... These techniques and procedures have been in use for many years and are among ... Parsa Mohebi, M.D. has utilized many of these methods over the years, he also ...
(Date:11/30/2015)... ... November 30, 2015 , ... The presidential race normally ... styling. So why is it a national news story when Donald Trump makes disparaging ... M.D., because appearances count more than anyone wants to admit when it comes to ...
(Date:11/30/2015)... , ... November 30, 2015 , ... According to Los ... people to overeat are not necessarily caused by real hunger, but instead by ... needs food. He notes that, while many patients are aware that weight loss surgery ...
Breaking Medicine News(10 mins):