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  • An orally bioavailable selective multikinase inhibitor of mutant forms, fusions and rearrangements involving the proto-oncogene receptor tyrosine kinase rearranged during transfection (RET) as well as the serine/threonine-protein kinase B-raf (BRAF), with potential antineoplastic activity. Upon oral administration, RET/BRAF multikinase inhibitor RXDX-105 selectively and potently binds to and targets various RET- and BRAF-containing mutants, fusions and rearrangements. This results in inhibition of cell growth in tumors cells that exhibit increased RET and BRAF activity. RET overexpression, activating mutations, and fusions result in the upregulation and/or overactivation of RET tyrosine kinase activity in various cancer cell types; dysregulation of RET activity plays a key role in the development and progression of these cancers. BRAF, a member of the raf family of serine/threonine protein kinases, plays a role in the regulation of MAP kinase/ERK signaling pathways, which may be constitutively activated in certain cancer cells with activating BRAF gene mutations.
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