Definition

An orally bioavailable type II protein kinase inhibitor of multiple kinases, including c-Met (hepatocyte growth factor receptor; HGFR), FMS-like tyrosine kinase-3 (FLT3; CD135; fetal liver kinase-2; Flk2), tropomyosin-related-kinase (tyrosine receptor kinase; TRK), and cyclin-dependent kinases 8 and 19 (CDK8/19), with potential antineoplastic and immunomodulating activities. Upon oral administration, c-Met/FLT3/TRK/CDK8/19 inhibitor TSN084 targets, binds to and inhibits the activity of various kinases, such as c-Met, FLT3, TRK and CDK8/19, and prevents activation of oncogenic signaling pathways mediated by these kinases, blocks selective transcription of various tumor-promoting genes, and inhibits proliferation of susceptible tumor cells that overexpress these kinases. These kinases are overexpressed or mutated in certain cancer cell types and play key roles in tumor cell proliferation, survival, invasion, treatment resistance and immune evasion.