Glumetinib (SCC 244) is a novel potent and highly selective inhibitor of c-Met kinase with IC50 of 0.42 nM; displays high selectivity versus 312 other tested protein kinases; profoundly and specifically inhibits c-Met signal transduction and suppresses the c-Met-dependent neoplastic phenotype of tumor and endothelial cells; exhibits robust in vivo antitumor activity in NSCLC and hepatocellular carcinoma models.

PLB-1001 (Bozitinib, PLB1001, CBI-3103, CBT-101) is a potent, highly selective, ATP-competitive, BBB-permeable MET kinase inhibitor, potently inhibits MET activity by 95.1% at 2 uM; Similar with crizotinib, PLB-1001 inhibited the phosphorylation of MET and STAT3, indicating a robust inhibitory effect of PLB-1001 on MET and its downstream signaling pathways; demonstrates remarkable potency in selectively inhibiting MET-altered tumor cells (METex14) in preclinical models; also exhibits clinical potential for precisely treating gliomas.

AMG-458 (AMG458) is a potent, selective, orally bioavailable c-Met inhibitor with Ki of 1.2 nM (human c-Met); also potently binds to mutant c-Met (H1094R), c-Met (V1092I) and c-Met (D1228H) with Ki values of 0.5-2.2 nM; inhibits HGF-mediated c-Met phosphorylation in PC3 and CT26 cells with IC50 of 60 and 120 nM, abrogates the constitutive phosphorylation of c-Met in H441 cells; significantly inhibits tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models.

MK-8033 is a potent, specific, dual c-Met/Ron kinases inhibitor with IC50 of 1/7 nM, also potently inhibits oncogenic c-Met activation loop mutants Y1230C, Y1230H and Y1235D with IC50 of 0.6-1.2 nM; MK-8033 is >100-fold selective relative to Ron and c-Met inhibition against a panel of 221 kinases; potently and selectively inhibits growth in c-Met amplified cell lines (GTL-16 proliferation IC50 =582 nM), causes full inhibition of tumor growth in c-Met amplified (GTL-16) subcutaneous tumor xenograft model; synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth.

MK-8033 is a potent, specific, dual c-Met/Ron kinases inhibitor with IC50 of 1/7 nM, also potently inhibits oncogenic c-Met activation loop mutants Y1230C, Y1230H and Y1235D with IC50 of 0.6-1.2 nM; MK-8033 is >100-fold selective relative to Ron and c-Met inhibition against a panel of 221 kinases; potently and selectively inhibits growth in c-Met amplified cell lines (GTL-16 proliferation IC50 =582 nM), causes full inhibition of tumor growth in c-Met amplified (GTL-16) subcutaneous tumor xenograft model; synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth.

PF-04217903 is a potent, selective, ATP-competitive c-Met kinase inhibitor with Ki of 4.8 nM, inhibits HGF-stimulated tyrosine phosphorylation of wild type c-Met with IC50 of 7.3 nM in cell-based assays; shows similar potency for inhibition of c-Met phosphorylation in mIMCD3 mouse epithelial cells (IC50=6.9 nM) and MDCK cell (IC50=9.5 nM); also exhibits inhibitory activities against c-Met mutations including V1092I, H1094R, M1250T, R988C, and T11010I (IC50=530 nM), but has little to no activity against mutants Y1230C and Y1235D; inhibits tumor cell proliferation, survival, migration/invasion both in vitro and in vivo.

AMG-208 is a potent, small-molecule c-Met inhibitor with IC50 of 5.2 nM against wt MET kinase, also inhibits VEGFR2 with IC50 of 112 nM; inhibits HGF-mediated c-Met phosphorylation in PC3 cells with IC50 of 46 nM, suppresses proliferation and induces apoptosis in human tumor xenograft models.

SAR 125844 (SAR125844;SAR-125844) is a potent, highly selective, ATP-competitive MET receptor tyrosine kinase inhibitor with IC50 of 4.2 nM; also inhibits H1094Y, Y1235D, M1250T, L1195V, and D1228H mutants with IC50 of 0.22, 1.7, 6.5, 65, and 81 nM, respectively; displays >100-fold selectivity over RON, and good selectivity in a panel of 275 human kinases; inhibits phosphorylation of wild-type MET, M1250T, Y1235D, and L1195V MET mutants with IC50 of 8.8, 30, 179, and 591 nM, respectively; selectively inhibits proliferation in cells with MET gene amplification, promotes apoptosis and inhibits HGF-mediated tumor cell migration; displays potent antitumor activity in vivo models.

BMS-817378 is a prodrug of the dual Met/VEGFR-2 inhibitor BMS-794833.

BMS794833 is a potent ATP competitive inhibitor of Met/VEGFR2 with IC50 of 1.7 nM/15 nM; also inhibits Ron, Axl and Flt-3 with IC50<3 nM; shows selectivity over a panel of >200 RTKs, non-RTKs and serine/threonine kinases; inhibits the cell growth in GTL-16 gastric carcinomas with an IC50 of 39 nM; active in multiple tumor models.