Definition

An orally bioavailable, selective, second-generation inhibitor of the proto-oncogene receptor tyrosine kinase rearranged during transfection (RET), with potential antineoplastic activity. Upon oral administration, RET inhibitor TY-1091 selectively targets and binds to wild-type RET and various RET fusions and mutations, including, but not limited to solvent front and gatekeeper mutations RET G810S, RET V804M/L/E, RET V804M/G810S and M918T/G810S, thereby inhibiting the activity of RET. This results in an inhibition of cell growth of tumors that exhibit increased RET activity due to these fusions and mutations. RET overexpression, activating mutations, and fusions result in the upregulation and/or overactivation of RET tyrosine kinase activity in various cancer cell types. Dysregulated RET activity plays a key role in the development and progression of certain cancers. Solvent front and gatekeeper resistance mutations play a key role in acquired tumor resistance to RET inhibitors.