Simeprevir

• CAT Number: I005499
• CAS Number: 923604-59-5
• Molecular Formula: C₃₈H₄₇N₅O₇S₂
• Molecular Weight: 749.96
• Purity: ≥95%
• Target: HCV Protease
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 0.36 nM(Ki); 7.8 nM (EC50)
• InChI: InChI=1S/C38H47N5O7S2/c1-21(2)30-20-51-35(40-30)29-18-32(26-13-14-31(49-5)22(3)33(26)39-29)50-24-16-27-28(17-24)36(45)43(4)15-9-7-6-8-10-23-19-38(23,41-34(27)44)37(46)42-52(47,48)25-11-12-25/h8,10,13-14,18,20-21,23-25,27-28H,6-7,9,11-12,15-17,19H2,1-5H3,(
• InChIKey: JTZZSQYMACOLNN-VDWJNHBNSA-N
• SMILES: CC1=C(C=CC2=C1N=C(C=C2OC3CC4C(C3)C(=O)N(CCCCC=CC5CC5(NC4=O)C(=O)NS(=O)(=O)C6CC6)C)C7=NC(=CS7)C(C)C)OC

Simeprevir (TMC 435350) is a potent inhibitor of HCV NS3/4A protease (Ki = 0.36 nM) and viral replication (replicon EC50 = 7.8 nM). HCV
Simeprevir plays an important role in HCV replication. Data from phase I and II clinical trials of TMC-435350 (TMC 435350; TMC 435; TMC-435350) to date have shown that this agent is well tolerated as a once-daily oral therapy and provides potent antiviral activity in HCV genotype 1-infected subjects, with restoration of liver enzymes and no evidence of viral breakthrough.

Reference

[1]. Raboisson P, et al. Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4853-8.


[2]. Lin, Tse-I.; Lenz, Oliver; Fanning, Gregory; Verbinnen, Thierry; Delouvroy, Frederic; In vitro activity and preclinical profile of TMC435350, a potent hepatitis C virus protease inhibitor. Antimicrobial Agents and Chemotherapy (2009), 53(4), 1377-1385. 


[3]. Xue W, Pan D, Yang Y, Liu H, Yao X.Molecular modeling study on the resistance mechanism of HCV NS3/4A serine protease mutants R155K, A156V and D168A to TMC435.Antiviral Res. 2012 Jan;93(1):126-37. Epub 2011 Nov 22. 


[4]. Manns M, Reesink H, Berg T, Dusheiko G, Flisiak R, Marcellin P, Moreno C, Lenz O, Meyvisch P, Peeters M, Sekar V, Simmen K, Verloes R.Rapid viral response of once-daily TMC435 plus pegylated interferon/ribavirin in hepatitis C genotype-1 patients: a randomized trial.Antivir Ther. 2011;16(7):1021-33. 


[5]. Lin TI, Lenz O, Fanning G, Verbinnen T, Delouvroy F, Scholliers A, Vermeiren K, Rosenquist A, Edlund M, Samuelsson B, Vrang L, de Kock H, Wigerinck P, Raboisson P, Simmen K.In vitro activity and preclinical profile of TMC435350, a potent hepatitis C virus protease inhibitor.Antimicrob Agents Chemother. 2009 Apr;53(4):1377-85. Epub 2009 Jan 26.