Sunitinib (malate)

Sunitinib is a small molecule inhibitor of receptor tyrosine kinases, including FLK1 (Ki = 9 nM), PDGFRbeta (Ki = 8 nM), and FLT3. It is at least 10-fold selective for FLK1 and PDGFRbeta over a variety of tyrosine kinases in a panel, including EGFR, Cdk2, Met, IGFR-1, Abl, and Src. Sunitinib inhibits VEGF-dependent FLK1 and PDGF-dependent PDGFRbeta phosphorylation (IC50s = 10 and 10 nM, respectively) as well as phosphorylation of FLT3 and FLT3 carrying the activating internal tandem duplication mutation (FLT3-ITD, IC50s = 250 and 50 nM, respectively). It decreases VEGF- and FGF-induced proliferation of human umbilical vein endothelial cells (HUVECs, IC50s = 30 and 700 nM, respectively) and reduces tumor growth in a variety of mouse xenograft models when administered at doses ranging from 20 to 80 mg/kg per day. Formulations containing sunitinib have been used in the treatment of gastrointestinal stromal tumors and metastatic renal cell carcinoma.Formal Name: N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, (2S)-hydroxy-butanedioic acid. CAS Number: 341031-54-7. Synonyms: SU11248. Molecular Formula: C22H27FN4O2 . C4H6O5. Formula Weight: 532.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 1 mg/ml, DMSO: 5 mg/ml, DMSO:PBS(pH 7.2) (1:3): 0.25 mg/ml. lambdamax: 267, 427 nm. SMILES: CCN(CC)CCNC(=O)c1c(C)[nH]c(\C=C2\C(=O)Nc3ccc(F)cc/23)c1COC(=O)C[C@H](O)C(=O)O. InChi Code: InChI=1S/C22H27FN4O2.C4H6O5/c1-5-27(6-2)10-9-24-22(29)20-13(3)19(25-14(20)4)12-17-16-11-15(23)7-8-18(16)26-21(17)28,5-2(4(8)9)1-3(6)7/h7-8,11-12,25H,5-6,9-10H2,1-4H3,(H,24,29)(H,26,28),2,5H,1H2,(H,6,7)(H,8,9)/b17-12-,. InChi Key: LBWFXVZLPYTWQI-HBPAQXCTSA-N.