tepotinib + omeprazole

**tepotinib + omeprazole** is an experimental drug combination composed of tepotinib, a selective small-molecule inhibitor of the MET receptor tyrosine kinase, and omeprazole, a proton pump inhibitor that targets the vacuolar-type H+-ATPase (V-ATPase). This combination has shown synergistic antitumor activity in KRAS-mutant non-small cell lung cancer (NSCLC) cell lines, including those resistant to KRAS G12C inhibitors (such as sotorasib) and MEK inhibitors (such as trametinib). Mechanistically, tepotinib inhibits MET signaling, while omeprazole modulates the tumor microenvironment and intracellular pH by inhibiting V-ATPase, potentially sensitizing cancer cells to MET inhibition. Preclinical studies demonstrate this combination downregulates phosphorylation of glycolytic enzyme enolase 1 (ENO1), LRP5/6, ERK1/2, and MET, with enhanced efficacy versus either agent alone in in vitro and in vivo xenograft models. The combination is being explored as a therapeutic strategy in KRAS-mutant NSCLC, especially in resistant disease[1][3].

Brand names

Tabrecta

Other names

HMPAMSC2156119JMSC-2156119JMSC 2156119Jproton pump inhibitor + MET inhibitor