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
SMILES / InChI / InChIKey
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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
References
1. Alcedo KP, Thanigachalam S, Naser SA. (2016)
RHB-104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn's disease associated with Mycobacterium paratuberculosis.
Gut Pathog, 8: 32. [PMID:27307791]
2. Arbiser JL, Moschella SL. (1995)
Clofazimine: a review of its medical uses and mechanisms of action.
J Am Acad Dermatol, 32 (2 Pt 1): 241-7. [PMID:7829710]
3. Faouzi M, Starkus J, Penner R. (2015)
State-dependent blocking mechanism of Kv 1.3 channels by the antimycobacterial drug clofazimine.
Br J Pharmacol, 172 (21): 5161-73. [PMID:26276903]
4. HRSA. 
National Hansen's Disease (Leprosy) Program.
Accessed on 04/07/2016. Modified on 04/07/2016. HRSA- Health Resources and Services Administration, http://www.hrsa.gov/hansensdisease/
5. Savarino E, Bertani L, Ceccarelli L, Bodini G, Zingone F, Buda A, Facchin S, Lorenzon G, Marchi S, Marabotto E et al.. (2019)
Antimicrobial treatment with the fixed-dose antibiotic combination RHB-104 for Mycobacterium avium subspecies paratuberculosis in Crohn's disease: pharmacological and clinical implications.
Expert Opin Biol Ther, 19 (2): 79-88. [PMID:30574820]
6. Yuan S, Yin X, Meng X, Chan JF, Ye ZW, Riva L, Pache L, Chan CC, Lai PM, Chan CC et al.. (2021)
Clofazimine broadly inhibits coronaviruses including SARS-CoV-2.
Nature, [Epub ahead of print]. DOI: 10.1038/s41586-021-03431-4 [PMID:33727703]