Vandetanib

Vandetanib is a multi-kinase inhibitor that inhibits VEGFR2, VEGFR3, VEGFR1, EGFR, PDGFRbeta, Tie-2, and FGFR1 in cell-free assays (IC50s = 40, 110, 1,600, 500, 1,100, 2,500, and 3,600 nM, respectively). It also binds to 142 additional kinases in a panel of 442 kinases (Kds = 4.6-7,900 nM). Vandetanib (1 and 2.5 µM) induces apoptosis and cell cycle arrest at the G0/G1 phase in GEO colon and OVCAR-3 ovarian cancer cells. It inhibits proliferation of HAK1-B, KYN-2, and Huh7 hepatocarcinoma cells, as well as human umbilical vein endothelial cells (HUVECs), with IC50 values of 10, 8.1, 9.4, and 7.1 µM, respectively. Vandetanib (200 mg/kg) increases survival and decreases tumor angiogenesis and VEGFR2 levels in a D54MG glioblastoma mouse xenograft model. It reduces tumor growth in a variety of mouse xenograft models, including lung, colon, and breast cancer models, when administered at doses of 25, 50, and 100 mg/kg per day. Formulations containing vandetanib have been used in the treatment of medullary thyroid cancer.Formal Name: N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl)methoxy]-4-quinazolinamine. CAS Number: 443913-73-3. Synonyms: CH 331, Zactima, ZD 6474. Molecular Formula: C22H24BrFN4O2. Formula Weight: 475.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 2 mg/ml, DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml, DMSO: 2 mg/ml. lambdamax: 217, 250, 331 nm. SMILES: COC1=C(OCC2CCN(C)CC2)C=C3C(C(NC4=CC=C(Br)C=C4F)=NC=N3)=C1. InChi Code: InChI=1S/C22H24BrFN4O2/c1-28-7-5-14(6-8-28)12-30-21-11-19-16(10-20(21)29-2)22(26-13-25-19)27-18-4-3-15(23)9-17(18)24/h3-4,9-11,13-14H,5-8,12H2,1-2H3,(H,25,26,27). InChi Key: UHTHHESEBZOYNR-UHFFFAOYSA-N.