JNJ-38877618 (OMO-1) is an effective and highly selective inhibitor of Met kinase (IC50s: 2 and 3 nM for wild type and mutant Met, respectively).

MET (mutant):2 nM, MET (WT):2 nM

JNJ-38877618 shows nM potency against Met Ampl/mutant and therapy-resistant models. JNJ-38877618 has nM binding affinity (Kd=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 results in the 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. JNJ-38877618 causes 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. Combination treatments are well tolerated and improved EGFR targeted therapy[1].