SOMCL-863, a novel, selective and orally bioavailable small-molecule c-Met inhibitor, exhibits antitumor activity both in vitro and in vivo

• SOMCL-863 is a potent and highly selective c-Met inhibitor.
• SOMCL-863 blocks c-Met signaling across different c-Met activation mechanisms.
• SOMCL-863 suppresses c-Met-mediated invasive growth phenotype.
• SOMCL-863 inhibits c-Met-dependent tumor growth in vivo.
• SOMCL-863 inhibits c-Met-mediated angiogenic effects in vitro and in vivo.

Deregulation of HGF/c-Met signaling and its driven neoplastic phenotype are associated with a variety of human malignancies. We herein reported SOMCL-863 as a novel selective c-Met inhibitor which effectively abrogated c-Met signaling pathways, thereby leading to substantial impairment of c-Met-dependent cell proliferation, migration, invasion, cell scattering and invasive growth. In EBC-1 and NCI-H1993 xenografts, SOMCL-863 exerted significant anti-tumor efficacy through anti-proliferative effects and antiangiogenic mechanisms, including reduction of tumor cell proliferation and reductions of microvessel density and secretion of proangiogenic factor IL-8. Together with the optimal pharmacokinetic properties, SOMCL-863 is a promising candidate worthy for further evaluation as a treatment of c-Met-driven human cancers.