Ripretinib

Ripretinib is an inhibitor of KIT and PDGFRalpha (IC50s = 3 and 3.6 nM, respectively). It is selective for KIT and PDGFRalpha over a panel of 300 kinases (IC50s = >100 nM) but does inhibit DDR2, VEGFR2, PDGFRbeta, and Tie2 (IC50s = V654A, KITT670I, KITD816H, KITD816V, and PDGFRalphaD842V (IC50s = 11, 9.2, 18, 25, and 36 nM, respectively). Ripretinib induces apoptosis in ROSA wild-type, and KITD816V- or KITK509I-expressing mast cells in a concentration-dependent manner. It reduces tumor growth and increases survival in an imatinib-resistant patient-derived xenograft (PDX) mouse model of gastrointestinal stromal tumors (GISTs) when administered at doses of 50 and 100 mg/kg. Formulations containing ripretinib have been used in the treatment of GISTs.Formal Name: N-[4-bromo-5-[1-ethyl-1,2-dihydro-7-(methylamino)-2-oxo-1,6-naphthyridin-3-yl]-2-fluorophenyl]-N'-phenyl-urea. CAS Number: 1442472-39-0. Synonyms: DCC-2618. Molecular Formula: C24H21BrFN5O2. Formula Weight: 510.4. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: DMF: 1 mg/ml, DMSO: 1 mg/ml. lambdamax: 238, 261, 354 nm. SMILES: O=C(NC1=C(F)C=C(Br)C(C2=CC3=C(N(CC)C2=O)C=C(NC)N=C3)=C1)NC4=CC=CC=C4. InChi Code: InChI=1S/C24H21BrFN5O2/c1-3-31-21-12-22(27-2)28-13-14(21)9-17(23(31)32)16-10-20(19(26)11-18(16)25)30-24(33)29-15-7-5-4-6-8-15/h4-13H,3H2,1-2H3,(H,27,28)(H2,29,30,33). InChi Key: CEFJVGZHQAGLHS-UHFFFAOYSA-N.