MGCD-265

MGCD-265-analog (structurally related to MGCD-265) is an orally bioavailable multitargeted tyrosine kinase inhibitor with potential antineoplastic activity with IC50 of 29 nM and 10 nM for c-Met and VEGFR2, respectively.IC50 value:10 nM (VEGFR2), 29 nM(c-Met) [1]Target:VEGFR, c-Metin vivo: MGCD-265-analog has a reasonable half-life, 1.2 h in rats and 5.8 h in dogs, and has an acceptable clearance, 0.33 L/(kg h) in rats and 1.1 L/(kg h) in dogs. The steady state volume of distribution was low in rats (0.25 L/kg) and reasonable in dogs (1.5 L/kg), while the oral bio-availability was determined to be 12% and 42% in rats and dogs, respectively. GCD-265-analog performed well in vivo against a panel of different human tumor types, particularly those that are driven by or overexpress c-Met (MNNGHOS and MKN45). Tumor growth inhibition at a dose of 20 mg/kg po once daily ranged from 41% to 94%. MGCD-265-analog was found to show spill-over inhibition of a number of kinases in addition to the intended c-Met/VEGFR2 activity. MGCD-265-analog has significant antitumor activity in vivo.[1]

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> c-Met/HGFR

Research Areas >> Cancer

VEGFR2:10 nM (IC50)

c-Met:29 nM (IC50)

[1]. Claridge S, et al. Discovery of a novel and potent series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases. Bioorg Med Chem Lett. 2008 May 1;18(9):2793-8.

Nintedanib (BIBF 1120) | SU5416 | Apatinib Mesylate | PD173074 | Capmatinib (INCB28060) | Foretinib (GSK1363089) | PHA-665752 | SU 5402 | Linifanib (ABT-869) | Cediranib | Lucitanib | RAF265 (CHIR-265) | LY2784544 | BMS-777607 | SU14813