Evacetrapib

Evacetrapib is a benzazepine inhibitor of cholesteryl ester transfer protein (CETP, IC50s = 5.5 and 26 nM for human recombinant and plasma-derived proteins, respectively). It is selective for CETP over a panel of cell surface and nuclear receptors with no significant inhibition at 1 µM. Evacetrapib (1-10 µM) reduces expression of the serine protease proprotein convertase subtilisin kexin 9 (PCSK9) and the LDL receptor (LDLR) in HepG2 cells in a dose-dependent manner with no effect on cell viability. It also reduces protein levels of LDLR, SREBF2-M, and PCSK9 in HepG2 lysates, nuclear extracts, and culture medium, respectively, in a dose-dependent manner. Oral administration of evacetrapib (30 mg/kg) inhibits CETP activity by 98.5, 98.6, and 18.4% after four, eight, and 24 hours, respectively, in serum from transgenic mice expressing human CETP and ApoA1. Evacetrapib increases HDL cholesterol levels in CETP/ApoA1 transgenic mice in a dose-dependent manner, including by 129.7% eight hours following administration of a 30 mg/kg dose.Formal Name: trans-4-[[(5S)-5-[[[3,5-bis(trifluoromethyl)phenyl]methyl](2-methyl-2H-tetrazol-5-yl)amino]-2,3,4,5-tetrahydro-7,9-dimethyl-1H-1-benzazepin-1-yl]methyl]-cyclohexanecarboxylic acid. CAS Number: 1186486-62-3. Molecular Formula: C31H36F6N6O2. Formula Weight: 638.7. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, Ethanol: 30 mg/ml. lambdamax: 266 nm. SMILES: CN(N=N1)N=C1N([C@@H]2C(C=C(C)C=C3C)=C3N(C[C@@H]4CC[C@@H](C(O)=O)CC4)CCC2)CC5=CC(C(F)(F)F)=CC(C(F)(F)F)=C5. InChi Code: InChI=1S/C31H36F6N6O2/c1-18-11-19(2)27-25(12-18)26(5-4-10-42(27)16-20-6-8-22(9-7-20)28(44)45)43(29-38-40-41(3)39-29)17-21-13-23(30(32,33)34)15-24(14-21)31(35,36)37/h11-15,20,22,26H,4-10,16-17H2,1-3H3,(H,44,45)/t20-,22-,26-/m0/s1. InChi Key: IHIUGIVXARLYHP-YBXDKENTSA-N.