JNJ-38877618

JNJ-38877618 is a potent, highly selective, orally bioavailable Met kinase inhibitor with IC₅₀s of 2 and 3 nM for wild type and mutant Met, respectively. IC50 & Target: IC50: 2 nM (wt Met), 2 nM (mutant Met)^[1] In Vitro: OMO-1 (formerly JNJ-38877618), is a potent, highly selective, orally bioavailable Met kinase inhibitor with nM binding affinity (K_d=1.4 nM) and enzyme inhibitory activity against wt and M1268T mutant Met (2 and 3 nM IC₅₀). Met inhibitory effects are assessed in proliferation, colony formation and motility assays. JNJ-38877618 displays nM potency against Met Ampl/mutant and therapy resistant models^[1]. In Vivo: JNJ-38877618 induces complete inhibition of tumor growth in 3 models: the SNU5 Met amp gastric, U87-MG HGF autocrine glioblastoma and Hs746T Met exon 14 skipping mutant gastric cancer. JNJ-38877618 induces regression of large Met amplified EBC-1 SqNSCLC where JNJ-38877618 leads to dose- and time-dependent inhibition of Met kinase activation, with the duration of target shut down considerably exceeding plasma exposure times. Combination treatments are well tolerated and improved EGFR targeted therapy^[1].