Ripretinib

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.

Also known as 1-N'-[2,5-difluoro-4-[2-(1-methylpyrazol-4-yl)pyridin-4-yl]oxyphenyl]-1-N'-phenylcyclopropane-1,1-dicarboxamide, DCC 2618, DCC-2618, DCC2618, KIT/PDGFR Inhibitor DCC-2618, Qinlock, RIPRETINIB — per NCIT

Also identified as

• ATC L01EX19 per RXNORM
• NCIT NCIT:C124067 per NCIT
• SCTID 874906002 per RXNORM
• SCTID 876860008 per RXNORM
• UNII 9XW757O13D per RXNORM

Indications