Zibotentan

Zibotentan is a selective antagonist of the endothelin (ET) receptor type A (IC50s = 21 and >10,000 nM for human recombinant ETA and ETB, respectively). It inhibits growth of HEY, OVCA 433, SKOV3, and A2780 cells induced by endothelin 1 (ET-1, Cay-24127) in vitro. Zibotentan reduces ET-1-induced expression of MMP-2, MMP-9, VEGF, COX-1 and COX-2, mediators of cell invasion and angiogenesis, in HEY cells. In vivo, zibotentan (10-50 mg/kg per day) reduces tumor growth in an HEY mouse xenograft model in a dose-dependent manner. Formulations containing zibotentan are under clinical investigation for the treatment of ovarian and castration-resistant prostate cancers.Formal Name: N-(3-methoxy-5-methyl-2-pyrazinyl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]-3-pyridinesulfonamide. CAS Number: 186497-07-4. Synonyms: ZD 4054. Molecular Formula: C19H16N6O4S. Formula Weight: 424.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 10 mg/ml, DMSO: 10 mg/ml, DMSO:PBS (pH 7.2) (1:40): 0.02 mg/ml. lambdamax: 265 nm. SMILES: CC1=NC(OC)=C(NS(C2=CC=CN=C2C3=CC=C(C4=NN=CO4)C=C3)(=O)=O)N=C1. InChi Code: InChI=1S/C19H16N6O4S/c1-12-10-21-17(19(23-12)28-2)25-30(26,27)15-4-3-9-20-16(15)13-5-7-14(8-6-13)18-24-22-11-29-18/h3-11H,1-2H3,(H,21,25). InChi Key: FJHHZXWJVIEFGJ-UHFFFAOYSA-N.