Simeprevir

SKU: orb1223640

Description

A potent, orally available inhibitor of HCV NS3/4A protease with Ki of 0.36 nM, replicon EC50 of 7.8 nM; inhibits NS3/4A proteases of genotypes 1a and 1b with Ki of 0.5 and 0.4 nM, shows synergistic effect with α-Interferon and an NS5B inhibitor in the replicon model and additive with ribavirin; exerts favorable pharmacokinetic profile and antiviral activity in vivo.HCV Infection Approved(In Vitro):Simeprevir (TMC435) inhibits HCV in a dose-dependent manner in Huh7-Luc cells, with EC50 and EC90 values of 8 nM and 24 nM, respectively.Simeprevir (TMC435) inhibits NS3/4A proteases from HCV genotypes 1 to 6 with IC50s of 1/0.9/7/30/1.5/2.2/1.6 nM for 1a/1b/2b/3a/4/5/6, respectively.Simeprevir inhibits SARS-CoV-2 in Vero E6 cells with IC50s of 9.6±2.3 μM and 5.5±0.2 μM for Mpro and RdRp, respectively.(In Vivo):Simeprevir (TMC435) has moderate terminal elimination half-life (t1/2=1.5 h and 4.1 h for rat (3 mg/kg, p.o.), monkey (3 mg/kg, p.o.)).Simeprevir (TMC435350) exhibits a medium-slow rate of absorption, well distribution with the high concentration observed in the liver, and a low clearance.

Key Properties

• CAS Number: 923604-59-5
• MW: 749.9391
• Purity: >98% (HPLC)
• Formula: C₃₈H₄₇N₅O₇S₂
• 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
• Target: HCV
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Simeprevir (TMC435) has moderate terminal elimination half-life (t1/2 = 1.5 h and 4.1 h for rat (3 mg/kg, p.o.), monkey (3 mg/kg, p.o.)). Simeprevir (TMC435350) exhibits a medium-slow rate of absorption, well distribution with the high concentration observed in the liver, and a low clearance. Pharmacokinetic Parameters of Simeprevir (TMC435350) in male Sprague-Dawley rats. Animal model: Sprague-Dawley (SD) rats and cynomolgus monkeys. Dosage: 3 mg/kg. Administration: Oral administration. Result: Time at which peak concentration (Tmax) of 1 hour and 2 hour for rat and monkey, respectively. Concentration at 24 h after dosing (C24 h) of 0.9 and 2.3 ng/mL for rat and monkey, respectively. AUC0-24h = 1173 and1409 ng h/mL for rat and monkey, respectively.
• In Vitro:
  Simeprevir (TMC435) inhibits HCV in a dose-dependent manner in Huh7-Luc cells, with EC50 and EC90 values of 8 nM and 24 nM, respectively. Simeprevir (TMC435) inhibits NS3/4A proteases from HCV genotypes 1 to 6 with IC50s of 1/0.9/7/30/1.5/2.2/1.6 nM for 1a/1b/2b/3a/4/5/6, respectively. Simeprevir inhibits SARS-CoV-2 in Vero E6 cells with IC50s of 9.6±2.3 μM and 5.5±0.2 μM for Mpro and RdRp, respectively.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

TMC-435 | TMC435 | TMC435350 | TMC-435350

Quick Database Links

Gene Symbol

HCV