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 anti-mycobacterial action (possibly via DNA binding) but is no longer perscribed in the US. It also has 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 [3].

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 [6]. 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.
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2D Structure
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Physico-chemical Properties
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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
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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
Bioactivity Comments
The in vitro EC50 of clofazimine against SARS-CoV-2 is 0.31 μM in Vero E6 cells [6]. The comparable EC50 for MERS-CoV infection is 1.48 μM. Clofazimine reduces infection by SARS-CoV-2 and MERS-CoV in primary human cells and in an animal model. It did not modulate the protease activity of either Mpro or PLpro which are critical for cleaving the viral polypeptide.
Ligand mentioned in the following text fields