OSI-930

OSI-930 is a potent inhibitor of Kit, KDR and CSF-1R with IC50 of 80 nM, 9 nM and 15 nM, respectively; also potent to Flt-1, c-Raf and Lck and low activity against PDGFRα/β, Flt-3 and Abl.IC50 value: 9 nM(VEGFR2); 15 nM(CSF1R); 80 nM (Kit activated) [1]Target: VEGFR2/Kit/CSF1Rin vitro: OSI-930 inhibits the cell proliferation in the HMC-1 cell line with IC50 of 14 nM without significant effect on growth of the COLO-205 cell line that does not express a constitutively active mutant receptor tyrosine kinase. Moreover, OSI-930 also induces apoptosis in HMC-1 cell line with EC50 of 34 nM [1]. A recent study shows that OSI-930 inactivates purified, recombinant cytochrome P450 (P450) 3A4 with a Ki of 24 μM in a time- and concentration-dependent mode [2].in vivo: OSI-930, administrated at the maximally efficacious dose of 200 mg/kg by oral gavage, exhibits potent antitumor activity in a broad range of preclinical xenograft models including HMC-1, NCI-SNU-5, COLO-205 and U251 xenograft models [1].

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> c-Fms

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> c-Kit

Research Areas >> Cancer

[1]. Garton AJ, et al. 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, 66(2):1015-1024.

[2]. Lin HL, et al. Inactivation of cytochrome P450 (P450) 3A4 but not P450 3A5 by OSI-930, a thiophene-containing anticancer drug. Drug Metab Dispos. 2011, 39(2), 345-350.

Pexidartinib | Nintedanib (BIBF 1120) | SU5416 | Apatinib Mesylate | BLZ945 | PD173074 | Foretinib (GSK1363089) | SU 5402 | Linifanib (ABT-869) | Cediranib | Lucitanib | Masitinib (AB1010) | RAF265 (CHIR-265) | LY2784544 | SU14813