NCIt related terms : KIT/PDGFR Inhibitor DCC-2618;
NCIt definition : An orally bioavailable switch pocket control inhibitor of wild-type and mutated forms
of the tumor-associated antigens (TAA) mast/stem cell factor receptor (SCFR) KIT and
platelet-derived growth factor receptor alpha (PDGFR-alpha; PDGFRa), with potential
antineoplastic activity. Upon oral administration, ripretinib targets and binds to
both wild-type and mutant forms of KIT and PDGFRa specifically at their switch pocket
binding sites, thereby preventing the switch from inactive to active conformations
of these kinases and inactivating their wild-type and mutant forms. This abrogates
KIT/PDGFRa-mediated tumor cell signaling and prevents proliferation in KIT/PDGFRa-driven
cancers. DCC-2618 also inhibits several other kinases, including vascular endothelial
growth factor receptor type 2 (VEGFR2; KDR), angiopoietin-1 receptor (TIE2; TEK),
PDGFR-beta and macrophage colony-stimulating factor 1 receptor (FMS; CSF1R), thereby
further inhibiting tumor cell growth. KIT and PDGFRa are tyrosine kinase receptors
that are upregulated or mutated in a variety of cancer cell types; mutated forms play
a key role in the regulation of tumor cell proliferation and resistance to chemotherapy.;