CLEMIZOLE PENICILLIN

US Previously Marketed

First approved in 1960

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H20ClN3.C16H18N2O4S
Molecular Weight	660.225
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClC1=CC=C(CN2C(CN3CCCC3)=NC4=CC=CC=C24)C=C1.[H][C@]56SC(C)(C)[C@@H](N5C(=O)[C@H]6NC(=O)CC7=CC=CC=C7)C(O)=O

InChI

InChIKey=GKPMEGXMKPQRTN-CBDIPHIASA-N

InChI=1S/C19H20ClN3.C16H18N2O4S/c20-16-9-7-15(8-10-16)13-23-18-6-2-1-5-17(18)21-19(23)14-22-11-3-4-12-22;1-16(2)12(15(21)22)18-13(20)11(14(18)23-16)17-10(19)8-9-6-4-3-5-7-9/h1-2,5-10H,3-4,11-14H2;3-7,11-12,14H,8H2,1-2H3,(H,17,19)(H,21,22)/t;11-,12+,14-/m.1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23143674
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800030702 https://www.ncbi.nlm.nih.gov/pubmed/25140002

Clemizole is a drug in clinical development for the treatment of hepatitis C virus (HCV) infection. Clemizole is a novel inhibitor of TRPC5 channels. Clemizole is an H1 antagonist. Clemizole, an antihistamine drug that was once widely used for treatment of allergic disease, was recently discovered to be a potent inhibitor (IC50, 24 nM) of the interaction between an HCV protein (NS4B) and HCV RNA. Although clemizole was widely used during the 1950s and 1960s, this was before contemporary regulatory requirements were established for new drug development, and there is very minimal information about its pharmacokinetics and metabolism.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Transient receptor potential cation channel subfamily M member 5 6 Target ID: CHEMBL1628468 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25140002	Inhibitor 8297	1.0 µM [IC50]
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1358393	Antagonist 2778
Hepatitis C virus 22 Target ID: CHEMBL379 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20486856	Inhibitor 8297	8.0 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic disease 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14406465	Primary		Approved 8429	CLEMIZOLE Approved Use Allergic disease
Hepatitis C 42 Sources: http://adisinsight.springer.com/drugs/800030702	Primary		Phase I 428	Unknown Approved Use Unknown

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23143674	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		CLEMIZOLE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 991 CYP1A2 1054

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://jpet.aspetjournals.org/content/344/2/388 Page: 4.0	yes	A 5
CYP2C19 991	substrate 3367 Sources: https://jpet.aspetjournals.org/content/344/2/388 Page: 4.0	yes	A 5
CYP2C9 1037	substrate 3367 Sources: https://jpet.aspetjournals.org/content/344/2/388 Page: 4.0	yes
CYP2C9 1037	substrate 3367 Sources: https://jpet.aspetjournals.org/content/344/2/388 Page: 4.0	yes	A 5
CYP2D6 1217	substrate 3367 Sources: https://jpet.aspetjournals.org/content/344/2/388 Page: 4.0	yes	A 5
CYP3A4 1737	substrate 3367 Sources: https://jpet.aspetjournals.org/content/344/2/388 Page: 4.0	yes	A 5
CYP3A4 1737	substrate 3367 Sources: https://jpet.aspetjournals.org/content/344/2/388 Page: 4,5	yes		likely (co-administration study) Comment: When coadministered with ritonavir (CYP3A4 inhibitor), decreased the amount of the human-predominant clemizole metabolites (M1 and M6) Sources: https://jpet.aspetjournals.org/content/344/2/388 Page: 4,5

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241390/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:52140	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:52140
ChemicalBook	CB3875322	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3875322
MolPort	MolPort-000-411-312	https://www.molport.com/shop/molecule-link/MolPort-000-411-312
ZINC	ZINC000000057260	http://zinc15.docking.org/substances/ZINC000000057260

PubMed

Title	Date	PubMed
		252161010
[Antimycobacterial antihistaminics].	1989 Aug	2513793
Application of capillary electrophoresis to the determination of various benzylpenicillin salts.	2004 Apr 2	15065804
[Current syphilis therapies and serological control. Commentary on the article by M. Hartmann in Hautarzt, Volume 2 (2004)].	2004 Nov	15448930
Discovery of a hepatitis C target and its pharmacological inhibitors by microfluidic affinity analysis.	2008 Sep	18758449
New strategies for the treatment of hepatitis C virus infection and implications of resistance to new direct-acting antiviral agents.	2010	21694902
Antiviral therapy for hepatitis C virus: beyond the standard of care.	2010 Apr	21994657
The hepatitis C virus (HCV) NS4B RNA binding inhibitor clemizole is highly synergistic with HCV protease inhibitors.	2010 Jul 1	20486856
The Future of HCV Therapy: NS4B as an Antiviral Target.	2010 Nov	21157574
Green tea catechin, epigallocatechin gallate, suppresses signaling by the dsRNA innate immune receptor RIG-I.	2010 Sep 22	20877565
Chemical genetics-based discovery of indole derivatives as HCV NS5B polymerase inhibitors.	2014 Mar 21	24561671

Patents

Sample Use Guides

In Vivo Use Guide

100 mg Clemizole Hydrochloride Administered Orally Twice a Day for 28 Days

Route of Administration: Oral

In Vitro Use Guide

The contractile response to histamine was antagonized by the histamine H1-receptor antagonist, clemizole (0.1 uM), in human isolated myometrial strips. Clemizole (0.1 nM to 10 nM) competitively antagonized the contractile effect of 2-pyridylethylamine.

Name

Type

Language

CLEMIZOLE PENICILLIN

Official Name

English

BENZYLPENICILLIN COMBINED WITH 1-P-CHLOROBENZYL-2-(1-PYRROLIDINYLMETHYL)BENZIMIDAZOLE

Common Name

English

CLEMIZOLE PENICILLIN [MART.]

Common Name

English

CLEMIZOLPENICILLIN

Common Name

English

PENICILLIN G MIXTURE WITH CLEMIZOLE [MI]

Common Name

English

Clemizole penicillin [WHO-DD]

Common Name

English

clemizole penicillin [INN]

Common Name

English

CLEMIZOL-PENICILLIN GRUNENTHAL

Brand Name

English

PENICILLIN G MIXTURE WITH CLEMIZOLE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29578