Other receptor tyrosine kinases inhibited by merestinib

Merestinib (LY2801653) is a potent, orally bioavailable, multi-kinase inhibitor that targets a specific profile of receptor tyrosine kinases (RTKs). While its primary targets are MET (Hepatocyte Growth Factor Receptor) and MST1R (RON), it also exhibits significant inhibitory activity against a broader set of RTKs including the TAM family (AXL, MERTK, TYRO3), ROS1, DDR1, DDR2, TEK (TIE2), and FLT3 (Yan et al., 2013; He et al., 2019). These kinases are frequently dysregulated in various malignancies and contribute to tumor growth, survival, and the development of resistance to other targeted therapies. By inhibiting this array of RTKs, merestinib disrupts multiple downstream signaling pathways such as PI3K/AKT and MAPK/ERK, which are essential for oncogenesis and metastasis (Walsh et al., 2016). The drug is primarily investigated for its potential in treating solid tumors, particularly those characterized by MET alterations or resistance to EGFR inhibitors. Its multi-target nature allows it to address the complexity of tumor signaling and potential bypass mechanisms that lead to treatment failure (ClinicalTrials.gov, NCT01285037). The drug acts as a Type II ATP-competitive inhibitor, binding to the inactive conformation of the kinase domain to prevent phosphorylation and downstream signaling.

Other names

Secondary receptor tyrosine kinase targets of merestinibMerestinib-sensitive receptor tyrosine kinasesLY2801653 secondary targets

Type II ATP-competitive inhibition of the kinase domain