OSI-930

OSI-930 is a novel, potent inhibitor of Flt1, kinase insert domain receptor (KDR), CSF-1R, Lck, c-Raf and activated receptor tyrosine kinases Kit with IC50 values of 8, 9, 15, 22, 41 and 80 nM, respectively [1].

OSI-930 has been demonstrated to inhibit proliferation and induce apoptosis in the HMC-1 cell line which is highly dependent on Kit signaling for survival. On the contrary, OSI-930 revealed no growth inhibition of COLO-205 cell line under normal culture conditions [1].

OSI-930 has shown to time- and concentration-dependently inactivate P450 3A4. Additionally, OSI-930 could reduce CO difference spectra of P450 3A4 [2].

References:
[1] Garton AJ1, Crew AP, Franklin M, Cooke AR, Wynne GM, Castaldo L, Kahler J, Winski SL, Franks A, Brown EN, Bittner MA, Keily JF, Briner P, Hidden C, Srebernak MC, Pirrit C, O'Connor M, Chan A, Vulevic B,Henninger D, Hart K, Sennello R, Li AH, Zhang T, Richardson F, Emerson DL, Castelhano AL, Arnold LD,Gibson NW. OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models. Cancer Res. 2006 Jan 15;66(2):1015-24.
[2] Lin HL1, Zhang H, Medower C, Hollenberg PF, Johnson WW. Inactivation of cytochrome P450 (P450) 3A4 but not P450 3A5 by OSI-930, a thiophene-containing anticancer drug. Drug Metab Dispos. 2011 Feb;39(2):345-50.