EMD 1214063 is a potent and selective c-Met inhibitor with IC50 of 4 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. Phase 1.
AZD9291 is an oral, irreversible, and mutant-selective EGFR inhibitor with IC50 of 12.92, 11.44 and 493.8 nM for Exon 19 deletion EGFR, L858R/T790M EGFR, and WT EGFR, respectively. Phase 3.
CO-1686 is an irreversible, mutant-selective EGFR inhibitor with Ki of 21.5 nM and 303.3 nM for EGFRL858R/T790M and EGFRWT, respectively. Phase 2.
Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM, respectively.
PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM, >50-fold selectivity for c-Met than RTKs or STKs.
Tivantinib (ARQ 197)
Tivantinib (ARQ 197) is the first non-ATP-competitive c-Met inhibitor with Ki of 0.355 μM, little activity to Ron, and no inhibition to EGFR, InsR, PDGFRα or FGFR1/4. Phase 3.
Features:The first selective c-Met inhibitor to be advanced into human clinical trials.
SU11274 is a selective Met inhibitor with IC50 of 10 nM, no effects on PGDFRβ, EGFR or Tie2.
BMS-777607 is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC50 of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM, 40-fold more selective for Met-related targets versus Lck, VEGFR-2, and TrkA/B, and more than 500-fold greater selectivity versus all other receptor and non receptor kinases. Phase 1/2.
Features:A potent inhibitor of the Met family, and >40-fold selectivity vs. Lck, VEGFR2, and TrkA/B and >500-fold selective vs. other receptor and non-receptor kinases.
INCB28060 is a novel, ATP-competitive inhibitor of c-MET with IC50 of 0.13 nM, inactive against RONβ, as well as EGFR and HER-3. Phase 1.
Features:Inactive against RONβ, another member of the c-MET RTK family, as well as EGFR and HER-3 (members of the EGFR RTK family).
PF-04217903 is a selective ATP-competitive c-Met inhibitor with IC50 of 4.8 nM, susceptible to oncogenic mutations (no activity to Y1230C mutant). Phase 1.