clofazimine   Click here for help

GtoPdb Ligand ID: 9184

Synonyms: Lamprene®
Approved drug Immunopharmacology Ligand
clofazimine is an approved drug (FDA (1986))
Compound class: Synthetic organic
Comment: Clofazimine is a phenazine dye with antimycobacterial properties [3]. It has both antibacterial and anti-inflammatory activities. State-dependent block of Kv1.3 channels by clofazimine offers therapeutic potential for selective immunosuppression in the context of autoimmune diseases in which Kv1.3-expressing T cells play a significant role [4].

SARS-CoV-2: A report in Nature has identified that clofazimine has anti-coronavirus activity, and that this is synergistic with the antiviral activity of remdesivir [7]. The drug was found to inhibit viral spike-mediated cell fusion and viral helicase activity in vitro, which translated to reduced pulmonary viral load, gut viral shedding and inflammation in an in vivo infection model. The authors suggest that their data supports the use of clofazimine in an outpatient setting for those infected with SARS-CoV-2, or for hospitalised COVID-19 patients if combined with remdesivir. Based on this evidence it is planned to progress clofazimine + remdesivir directly into Phase 2 clinical trial. A trial of clofazimine + interferon-1β is already underway.

clofazimine is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 41.69
Molecular weight 472.12
XLogP 8.81
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Clc1ccc(cc1)Nc1cc2nc3ccccc3n(c2cc1=NC(C)C)c1ccc(cc1)Cl
Isomeric SMILES Clc1ccc(cc1)Nc1cc2nc3ccccc3n(c2cc1=NC(C)C)c1ccc(cc1)Cl
InChI InChI=1S/C27H22Cl2N4/c1-17(2)30-24-16-27-25(15-23(24)31-20-11-7-18(28)8-12-20)32-22-5-3-4-6-26(22)33(27)21-13-9-19(29)10-14-21/h3-17,31H,1-2H3
InChI Key WDQPAMHFFCXSNU-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Clofazimine is used in combination with the antibacterials, rifampicin and dapsone, as multidrug therapy (MDT) for the treatment of leprosy [2].
Clofazimine is on the World Health Organisation's List of Essential Medicines. It is not commercially available in the US, but can been obtained from the National Hansen's Disease (Leprosy) Program (NHDP) of the US Department of Health and Human Services when required [5].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Clofazimine inhibits bacterial DNA replication and proliferation [2].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04465695 Dual Therapy With Interferon Beta-1b and Clofazimine for COVID-19 Phase 2 Interventional The University of Hong Kong
NCT03009396 Open Label Efficacy and Safety of Anti-MAP (Mycobacterium Avium Ssp. Paratuberculosis) Therapy in Adult Crohn's Disease Phase 3 Interventional RedHill Biopharma Limited RHB-104 is a fixed-dose combination of clofazimine, and rifabutin. This was evaluated as a therapy for treating Crohn's disease associated with Mycobacterium avium subspecies paratuberculosis (MAP). 1,6
External links Click here for help
For extended ADME data see the following:

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