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  • DC Chemicals Limited
  • China
  • Product Name: TMC435
  • Price: $Inquiry/100mg $Inquiry/250mg $Inquiry/500mg
  • Purity: 98.0%
  • Stocking Period: 3 Day
  • Contact: Tony Cao


1241946-89-3

1241946-89-3 structure
1241946-89-3 structure
  • Name: TMC435
  • Chemical Name: TMC 435 sodium salt
  • CAS Number: 1241946-89-3
  • Molecular Formula: C38H46N5NaO7S2
  • Molecular Weight: 771.92100
  • Catalog: Signaling Pathways Anti-infection HCV
  • Create Date: 2017-04-26 00:28:38
  • Modify Date: 2024-01-10 14:33:30
  • Simeprevir (TMC435; TMC435350) sodium is an oral, potent and highly specific hepatitis C virus (HCV) NS3/4A protease inhibitor with a Ki of 0.36 nM. Simeprevir sodium inhibits HCV replication with an EC50 of 7.8 nM. Simeprevir sodium also potently suppresses SARS-CoV-2 replication and synergizes with Remdesivir. Simeprevir sodium inhibits the main protease (Mpro) and the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, and also modulates host immune responses[1][4].

Name TMC 435 sodium salt
Synonyms Simeprevir sodium
TMC 435 sodium
Sovriad
Description Simeprevir (TMC435; TMC435350) sodium is an oral, potent and highly specific hepatitis C virus (HCV) NS3/4A protease inhibitor with a Ki of 0.36 nM. Simeprevir sodium inhibits HCV replication with an EC50 of 7.8 nM. Simeprevir sodium also potently suppresses SARS-CoV-2 replication and synergizes with Remdesivir. Simeprevir sodium inhibits the main protease (Mpro) and the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, and also modulates host immune responses[1][4].
Related Catalog
Target

Ki: 0.36 nM (HCV NS3/4A protease)[1] EC50: 7.8 nM (HCV replication)[1] IC50: 9.6±2.3 μM (SARS-CoV-2 Mpro), 5.5±0.2 μM (SARS-CoV-2 RdRp)[4]

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[2]. 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[3]. Simeprevir inhibits SARS-CoV-2 in Vero E6 cells with an IC50 of 9.6±2.3 μM and 5.5±0.2 μM for Mpro and RdRp, respectively[4].
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.))[3]. Simeprevir (TMC435350) exhibits a medium-slow rate of absorption, well distribution with the high concentration observed in the liver, and a low clearance[1]. Pharmacokinetic Parameters of Simeprevir (TMC435350) in male Sprague-Dawley rats[1]. IV (2 mg/kg) PO (10 mg/kg) CL (L/h/kg) 0.505 Vdss (h) 0.49 AUC0-24 (μM·h) 5.21 2.79 Cmax (μM) 0.73 Tmax (h) 3.0 T1/2 (h) 2.8 F (%) 11 Liver/plasma ratio at 6 h 63.5 32 Animal Model: Sprague-Dawley (SD) rats and cynomolgus monkeys[3] Dosage: 3 mg/kg Administration: PO; single dosage 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 and 1409 ng·h/mL for rat and monkey, respectively.
References

[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 TI, et al. 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.

[3]. Rajagopalan R, et al. Preclinical Characterization and Human Microdose Pharmacokinetics of ITMN-8187, a Nonmacrocyclic Inhibitor of the Hepatitis C Virus NS3 Protease. Antimicrob Agents Chemother. 2016 Dec 27;61(1). pii: e01569-16.

[4]. Lo HS, et al. Simeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir. ACS Cent Sci. 2021 May 26;7(5):792-802.

Molecular Formula C38H46N5NaO7S2
Molecular Weight 771.92100
Exact Mass 771.27400
PSA 184.97000
LogP 7.22770