The Preclinical Pharmacology of Tepotinib-A Highly Selective MET Inhibitor with Activity in Tumors Harboring MET Alterations.

ABSTRACT: The mesenchymal-epithelial transition factor (MET) proto-oncogene encodes the MET receptor tyrosine kinase. MET aberrations drive tumorigenesis in several cancer types through a variety of molecular mechanisms, including MET mutations, gene amplification, rearrangement, and overexpression. Therefore, MET is a therapeutic target and the selective type Ib MET inhibitor, tepotinib, was designed to potently inhibit MET kinase activity. In vitro, tepotinib inhibits MET in a concentration-dependent manner irrespective of the mode of MET activation, and in vivo, tepotinib exhibits marked, dose-dependent antitumor activity in MET-dependent tumor models of various cancer indications. Tepotinib penetrates the blood-brain barrier and demonstrates strong antitumor activity in subcutaneous and orthotop

SUBMITTER: Albers J 

PROVIDER: S-EPMC10320478 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature