LOMIBUVIR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H35NO4S
Molecular Weight	445.615
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H]1CC[C@@H](CC1)C(=O)N([C@H]2CC[C@H](O)CC2)C3=C(SC(=C3)C#CC(C)(C)C)C(O)=O

InChI

InChIKey=WPMJNLCLKAKMLA-VVPTUSLJSA-N

InChI=1S/C25H35NO4S/c1-16-5-7-17(8-6-16)23(28)26(18-9-11-19(27)12-10-18)21-15-20(13-14-25(2,3)4)31-22(21)24(29)30/h15-19,27H,5-12H2,1-4H3,(H,29,30)/t16-,17-,18-,19-

HIDE SMILES / InChI

Molecular Formula	C25H35NO4S
Molecular Weight	445.615
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24982088
Curator's Comment: Description was created based on several sources, including http://en.pharmacodia.com/web/drug/1_819.html http://adisinsight.springer.com/drugs/800029330

Lomibuvir (VCH-222) is a novel, potent and selective inhibitor of non-nucleoside polymerase of the hepatitis C virus (HCV) RNA-dependent RNA polymerase, with an IC50 range of 0.94-1.2 μM. Lomibuvir was generated from ViroChem's research programme investigating HCV NS5B polymerase inhibitors. In phase 1 and 2 clinical studies, Lomibuvir demonstrated effective antiviral efficacy, with substantial reductions in plasma HCV RNA in patients chronically infected with genotype 1 HCV. On 15 May 2014 Vertex Pharmaceuticals completes a phase II trial in Hepatitis C (treatment-naive, combination therapy) in USA, Canada, Germany, Poland and United Kingdom (NCT01516918). On 26 Jul 2016 Trek Therapeutics acquires lomibuvir from Vertex Pharmaceuticals.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
NS5B protein 1 Target ID: CHEMBL2366503 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24982088	Inhibitor 8297		0.94 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hepatitis C 42 Sources: https://clinicaltrials.gov/ct2/show/NCT00911963	Primary		Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363680122	inconclusive [IC50 23.9185 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363680122	no
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363680122	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363680122	yes

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P008U19	https://www.1pchem.com/search?query=1P008U19
Compound Cloud	24798764
Excenen	EX-A1758	http://www.excenen.com/searchresultlist.php?id=EX-A1758
MolPort	MolPort-044-193-860	https://www.molport.com/shop/molecule-link/MolPort-044-193-860
Molcore	MC34093	http://www.molcore.com/CatMC34093.html
Molnova	M10130	https://www.molnova.com/en/serch-list.html?keywords=M10130
MuseChem	I007687	https://www.musechem.com/product/I007687.html
TargetMol	T6729	https://www.targetmol.com/search?keyword=T6729
eMolecules	300465659	https://orderbb.emolecules.com/search/#?query=300465659
eMolecules	49227228	https://orderbb.emolecules.com/search/#?query=49227228

PubMed

Title	Date	PubMed
Tegobuvir (GS-9190) potency against HCV chimeric replicons derived from consensus NS5B sequences from genotypes 2b, 3a, 4a, 5a, and 6a.	2012 Jul 20	22543048
Preclinical characterization of GS-9669, a thumb site II inhibitor of the hepatitis C virus NS5B polymerase.	2013 Feb	23183437
Restoration of the activated Rig-I pathway in hepatitis C virus (HCV) replicon cells by HCV protease, polymerase, and NS5A inhibitors in vitro at clinically relevant concentrations.	2013 Sep	23836176
Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug.	2014	24419349

Patents

Sample Use Guides

In Vivo Use Guide

100 or 400 mg twice daily

Route of Administration: Oral

In Vitro Use Guide

Lomibuvir exhibits antiviral activity against genotypes 1a, 1b, and 2a in the HCV replicon, with 50% effective concentrations (EC50s) ranging from 4.6 to 22.3 nM

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:48:18 UTC 2023` Edited by `admin` on `Sat Dec 16 01:48:18 UTC 2023`
Record UNII	37L2LF4A2D
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

LOMIBUVIR

Official Name

English

VCH-222

Code

English

5-(3,3-DIMETHYL-1-BUTYNYL)-3-((TRANS-4-HYDROXYCYCLOHEXYL)((TRANS-4-METHYLCYCLOHEXYL)CARBONYL)AMINO)THIOPHENE-2-CARBOXYLIC ACID

Systematic Name

English

LOMIBUVIR [USAN]

Common Name

English

Lomibuvir [WHO-DD]

Common Name

English

lomibuvir [INN]

Common Name

English

VX-222

Code

English

2-THIOPHENECARBOXYLIC ACID, 5-(3,3-DIMETHYL-1-BUTYN-1-YL)-3-((TRANS-4- HYDROXYCYCLOHEXYL)((TRANS-4-METHYLCYCLOHEXYL)CARBONYL)AMINO)-

Common Name

English

Code System Code Type Description

ChEMBL

CHEMBL3039503