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Details

Stereochemistry ACHIRAL
Molecular Formula C32H38N4O6S
Molecular Weight 606.732
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TMC-647055

SMILES

COC1=CC2=C(C=C1)C3=C(C4CCCCC4)C5=C6C=C(C=C5)C(=O)NS(=O)(=O)N(C)CCOCCN(C)C(=O)C(CN36)=C2

InChI

InChIKey=UOBYJVFBFSLCTQ-UHFFFAOYSA-N
InChI=1S/C32H38N4O6S/c1-34-13-15-42-16-14-35(2)43(39,40)33-31(37)22-9-11-27-28(19-22)36-20-24(32(34)38)17-23-18-25(41-3)10-12-26(23)30(36)29(27)21-7-5-4-6-8-21/h9-12,17-19,21H,4-8,13-16,20H2,1-3H3,(H,33,37)

HIDE SMILES / InChI

Molecular Formula C32H38N4O6S
Molecular Weight 606.732
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

TMC647055 is a potent and selective nonnucleoside inhibitor of NS5B binding site 1 (NNI-1) with activity against most HCV genotypes. Binding of inhibitors to NNI-1 is purported to displace the flexible λ1 loop from its thumb domain binding site, perturbing the interaction between the NS5B polymerase finger and thumb domains and thereby locking the enzyme in an open inactive conformation. Janssen R&D Ireland (formerly Tibotec Pharmaceuticals) is developing TMC 647055 as an oral once-daily treatment for chronic hepatitis C virus infections. Phase II development is underway in Belgium, Germany and the US.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
4.1 nM [Kd]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
A phase I trial assessed the safety and tolerability of TMC 647055 administered as an oral solution for 6 days in increasing single doses from 100 mg to 3000 mg in fed conditions and in multiple oral doses (NCT01202825)
Route of Administration: Oral
In Vitro Use Guide
The frequency of resistant colony formation was determined in a colony formation assay using wild-type HCV genotype 1b replicon (Huh7-Luc) cells incubated in the presence of different concentrations of TMC647055, no resistant replicon cell colonies were observed with 1.5 μM TMC647055 alone, indicating complete clearance of the replicon from the cells.
Substance Class Chemical
Record UNII
11BD024G7J
Record Status Validated (UNII)
Record Version