[CAS NO. 923604-59-5] Simeprevir (TMC435)

Name: Simeprevir (TMC435)
Brand: Arctom Scientific
SKU: SLK-S5015

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PRODUCTS SPECIFICATIONS [923604-59-5]

Store

Catalog

SLK-S5015

Brand

Selleck

CAS

923604-59-5

DESCRIPTION [923604-59-5]

Overview

MDL	MFCD25563225
Molecular Weight	749.94
Molecular Formula	C38H47N5O7S2
SMILES	C(NS(=O)(=O)C1CC1)(=O)[C@]23[C@@](C2)(/C=C\CCCCN(C)C(=O)[C@]4([C@](C(=O)N3)(C[C@@H](OC=5C6=C(N=C(C5)C7=NC(C(C)C)=CS7)C(C)=C(OC)C=C6)C4)[H])[H])[H]

For research use only.

Storage

3 years,-20°C,powder
1 years,-80°C,in solvent

Shipping

Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Concentration Volume Mass	1 mg	5 mg	10 mg
1 mM	1.3334 mL	6.6672 mL	13.3344 mL
5 mM	0.2667 mL	1.3334 mL	2.6669 mL
10 mM	0.1333 mL	0.6667 mL	1.3334 mL
50 mM	0.0267 mL	0.1333 mL	0.2667 mL

Description

Simeprevir (TMC-435, TMC-435350) is a competitive, reversible, macrocyclic, noncovalent inhibitor that acts directly against the hepatitis C virus. It has a medium inhibitory concentration (IC50) <13 nM for all HCV NS3/4A enzymes(genotypes 1a, 1b, 2, 4, 5, and 6), but has an IC50 value of 37 nM for genotype 3.

Targets

HCV NS3/4A protease ^[1]

In vitro

Simeprevir exhibits potent inhibition on NS3/4A protease of genotypes 1a, 1b, 2, 4, 5, and 6, with a medium inhibitory concentration (IC50) <13 nM for all HCV NS3/4A enzymes tested. However, the IC50 for genotype 3 is 37 nM. In vitro, simeprevir is also an inhibitor of bilirubin transporters OATP1B1 and MRP2. It is a more potent inhibitor of OATP1B1 (IC50=720 nM), which is primarily responsible for transporting unconjugated bilirubin, than MRP2 (IC50 around 10,000 nM), primarily a conjugated bilirubin transporter.

In vivo

In vivo, simeprevir has a relatively long absorption phase, reaching maximum concentration (Cmax) after 4-6 hours. It is extensively (99.9%) bound to plasma proteins, mainly to albumin. The absolute bioavailability is 44% after a single oral administration. In rats, The liver to blood ratio is 29:1, which means good distribution to the liver. For humans, in preclinical studies, the liver to plasma concentration ratio is really high (ratio of 39). The highest tissue/plasma AUC ratios are observed in the small intestine (ratio of 128). While tissue simeprevir concentrations reaches peak values within 4 hours postdosing, simeprevir concentrations in liver remains above the EC99 for up to 31 hours postdosing, and plasma concentrations are higher than the EC99 at 8 hours and around the EC50 at 24 hours postdosing. The AUC24h of simeprevir is increased by 61%-69% when administered with food. Simeprevir should therefore be taken with food. Simeprevir is also a substrate and inhibitor of P-glycoprotein. Simeprevir is metabolized by CYP3A4 and eliminated by biliary excretion. It is also an inhibitor of gut cytochrome 3A4 but not hepatic CYP3A4.

References

[1] Laure Izquierdo, et al. Pharmgenomics Pers Med. 2014, 7: 241-249.

Synonyms

Cyclopenta[c]cyclopropa[g][1,6]diazacyclotetradecine-12a(1H)-carboxamide, N-(cyclopropylsulfonyl)-2,3,3a,4,5,6,7,8,9,11a,12,13,14,14a-tetradecahydro-2-[[7-methoxy-8-methyl-2-[4-(1-methylethyl)-2-thiazolyl]-4-quinolinyl]oxy]-5-methyl-4,14-dioxo-, (2R,3aR,10Z,11aS,12aR,14aR)-

(2R,3aR,10Z,11aS,12aR,14aR)-N-(Cyclopropylsulfonyl)-2,3,3a,4,5,6,7,8,9,11a,12,13,14,14a-tetradecahydro-2-[[7-methoxy-8-methyl-2-[4-(1-methylethyl)-2-thiazolyl]-4-quinolinyl]oxy]-5-methyl-4,14-dioxocyclopenta[c]cyclopropa[g][1,6]diazacyclotetradecine-12a(1H)-carboxamide

TMC 435350

TMC 435

Simeprevir

Sovriad

Olysio

Merospevir