Definition

An orally bioavailable selective inhibitor of the proto-oncogene receptor tyrosine kinase rearranged during transfection (RET), with potential antineoplastic activity. Upon oral administration, RET inhibitor EP0031 selectively binds to various RET fusions and mutations, including solvent front resistance mutations, and inhibits 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. EP0031 is able to penetrate the blood-brain barrier (BBB) and may also be able to overcome resistance mechanisms to first generation selective RET inhibitors (SRIs).