Speaking of stupid acquisitions, there's also Cell Pathways. Given that their lead compound was already flopping when OSI bought it, what did they see? These?
>>Mol Cancer Ther. 2006;5:60-67
The sulindac derivatives OSI-461, OSIP486823, and OSIP487703 arrest colon cancer cells in mitosis by causing microtubule depolymerization
Danhua Xiao1, Atsuko Deguchi1, Gregg G. Gundersen2, Bert Oehlen3, Lee Arnold3 and I. Bernard Weinstein1
1 Herbert Irving Comprehensive Cancer Center and 2 Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York and 3 OSI Pharmaceuticals, Inc., Farmingdale, New York
Requests for reprints: I. Bernard Weinstein, Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University Medical Center, 701 West 168th Street, Room 1509, New York, NY 10032. Phone: 212-305-6921; Fax: 212-305-6889. E-mail: ibw1@columbia.edu
Exisulind (sulindac sulfone) and three highly potent derivatives, OSI-461 (CP461), OSIP486823 (CP248), and OSIP487703, inhibit growth and induce apoptosis in SW480 human colon cancer cells, with IC50s of 200, 2, 0.1, and 0.003 µmol/L, respectively. The latter three compounds, but not exisulind, induce marked M-phase cell cycle arrest in these cells. This effect seems to be independent of the known ability of these compounds to cause activation of protein kinase G. When tested at twice their IC50 concentration for growth inhibition, OSI-461, OSIP486823, and OSIP487703 cause depolymerization of microtubules in interphase cells, inhibit spindle formation in mitotic cells, and induce multinucleated cells. In vitro tubulin polymerization assays indicate that all three compounds interact with tubulin directly to cause microtubule depolymerization and/or inhibit de novo tubulin polymerization. These results suggest that the dual effects of OSI-461, OSIP486823, and OSIP487703 on impairment of microtubule functions and protein kinase G activation may explain the potent antiproliferative and apoptotic effects of these compounds in cancer cells.<<
Worth it? Probably not since these don't show up in OSI's oncology product chart. Not in the clinic yet after how many years? We know 461 is dead, these probably are, too. A publication good for resume padding only, I'd guess.
Cheers, Tuck |
