All time low today, not even a buck above cash. Are things really that bad at Kosan? Today had the feel of some institutional holders of small cap bios capitulating, liquidating. Kosan perhaps among them. Very tempted at these levels.
INFI and SNTA, which are the other players in this space outside of BIIB's Conforma program, are also near lows. Thought Hsp90 was supposed to be a hot target.
BIIB's Hsp90 program under the radar. They don't talk about their pipe much on the website, anyhow. CFN2024, which is an oral version is in P1:
clinicaltrials.gov
CFN1010, the original, has completed P1, but I haven't seen anything about advancing to P2.
Also Novartis has an Hsp90 inhibitor in P1-2: AUY922, which came from Vernalis.
>>J. Med. Chem., 51 (2), 196–218, 2008. 10.1021/jm701018h
Web Release Date: November 20, 2007
Copyright © 2008 American Chemical Society
4,5-Diarylisoxazole Hsp90 Chaperone Inhibitors: Potential Therapeutic Agents for the Treatment of Cancer
Paul A. Brough,*† Wynne Aherne,‡ Xavier Barril,† Jenifer Borgognoni,† Kathy Boxall,‡ Julie E. Cansfield,† Kwai-Ming J. Cheung,‡ Ian Collins,‡ Nicholas G. M. Davies,† Martin J. Drysdale,† Brian Dymock,† Suzanne A. Eccles,‡ Harry Finch,† Alexandra Fink,† Angela Hayes,‡ Robert Howes,† Roderick E. Hubbard,† Karen James,‡ Allan M. Jordan,† Andrea Lockie,† Vanessa Martins,‡ Andrew Massey,† Thomas P. Matthews,‡ Edward McDonald,‡ Christopher J. Northfield,† Laurence H. Pearl,‡ Chrisostomos Prodromou,‡ Stuart Ray,† Florence I. Raynaud,‡ Stephen D. Roughley,† Swee Y. Sharp,‡ Allan Surgenor,† D. Lee Walmsley,† Paul Webb,† Mike Wood,† Paul Workman,‡ and Lisa Wright†
Vernalis Ltd., Granta Park, Great Abington, Cambridge CB21 6GB, U.K., and Cancer Research U.K. Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, U.K.
Received August 15, 2007
Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential chemotherapeutic agents for cancer. Here, we describe the structure-based design, synthesis, structure-activity relationships and pharmacokinetics of potent small-molecule inhibitors of Hsp90 based on the 4,5-diarylisoxazole scaffold. Analogues from this series have high affinity for Hsp90, as measured in a fluorescence polarization (FP) competitive binding assay, and are active in cancer cell lines where they inhibit proliferation and exhibit a characteristic profile of depletion of oncogenic proteins and concomitant elevation of Hsp72. Compound 40f (VER-52296/NVP-AUY922) is potent in the Hsp90 FP binding assay (IC50 = 21 nM) and inhibits proliferation of various human cancer cell lines in vitro, with GI50 averaging 9 nM. Compound 40f is retained in tumors in vivo when administered i.p., as evaluated by cassette dosing in tumor-bearing mice. In a human colon cancer xenograft model, 40f inhibits tumor growth by ~50%.<<
And finally, Serenex has an oral one in P1, SNX-5422.
Kosan still leads, FWIW.
Cheers, Tuck |
