DCC-2618

DCC-2618 (Ripretinib, DCC2618) is a potent, oral inhibitor of singly and doubly mutated KIT with IC50 of WT (IC50=4 nM), V654A (8 nM), T670I (18 nM), D816H (5 nM), D816V; also inhibits PDGFRα/β, KDR and cFMS, robustly inhibits exon 17, exon 9/13, exon 9/14, and exon 9/17 KIT mutants, as well as exon 11/17 KIT mutants; inhibits wild type and mutant KIT phosphorylation in cancer cells, demonstrates the potential to treat KIT mutant-driven cancers including GIST, systemic mastocytosis, AML, or melanoma.Gastric Cancer Phase 3 Clinical (In Vitro) :Ripretinib (DCC-2618) suppresses phosphorylation of KIT and decreases the expression of phosphosphorylated (p) STAT5, pAKT and pERK1/2 in neoplastic mast cells. Ripretinib inhibits the growth of ROSAKIT K509I cells with an IC50 of 34 ± 10 nM, and also induces apoptosis in these cells. Ripretinib (0.1-1.0 μM) inhibits IgE-dependent histamine release from basophils and spontaneous tryptase release from neoplastic mast cells, and also counteracts growth and survival of leukemic monocytes and blast cells at 0.01-5 μM.Ripretinib (DCC-2618) is a pan-KIT and PDGFRA inhibitor, shows cytotoxic activity against gastrointestinal stromal tumors.