Clofazimine

Catalog No.S4107 Synonyms: NSC-141046

Clofazimine Chemical Structure

Molecular Weight(MW): 473.4

Clofazimine is a rhimophenazine dye, originally developed for the treatment of tuberculosis, it has both antimicrobial and antiinflammatory activity, postulated mechanisms of action include intercalation of clofazimine with bacterial DNA and increasing levels of cellular phospholipase A2.

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Biological Activity

Description Clofazimine is a rhimophenazine dye, originally developed for the treatment of tuberculosis, it has both antimicrobial and antiinflammatory activity, postulated mechanisms of action include intercalation of clofazimine with bacterial DNA and increasing levels of cellular phospholipase A2.
Features Intracellular activities of Clofazimine are superior to that of B4154.
Targets
PLA2 [1]
In vitro

Clofazimine stimulates oxygen consumption and superoxide generation by neutrophils, Clofazimine also causes phospholipase A2 activation in neutrophils, resulting in increased release of lysophosphatidylcholine and arachidonic acid from neutrophil membranes. Clofazimine inhibits mitogen-induced stimulation of peripheral blood mononuclear cells. Clofazimine stabilizes lysosomal membranes in macrophages and inhibits Mycobacterium leprae metabolism in mouse peritoneal macrophages. [1] Clofazimine (5 mg/mL) causes dose-related enhancement of the activity of phospholipase A2 in S. aureus, according to an increase in the release of 3H-radiolabeled arachidonate and lysophosphatidylethanolamine ([3H]LPE) from bacterial-membrane phospholipids. [2] Clofazimine inhibits 90% of twenty M. tuberculosis strains with MICs <1.0 μg/mL, to be noted, clofazimine inhibits M. tuberculosis strain 2227 with MICs of 0.06 μg/mL. Clofazimine (1 μg/mL) dose-dependently inhibits activity of J774A.1 macrophages. [3]

In vivo Clofazimine (20 mg/kg) prevents mortality and causes a significant reduction in the numbers of CFU in the lungs and spleens of C57BL/6 mice infected M.tuberculosis H37Rv. [3] Liposomal Clofazimine (L-CLF) (50 mg/kg) dose-dependently reduces CFU 2 to 3 log units in the spleen, liver, and lungs of acutely infected mice with Mycobacterium tuberculosis Erdman. [4] Clofazimine (500 μg, bid) results in highest Clofazimine concentrations in spleens and livers of mice whereas Clofazimine concentrations in the lungs are significantly lower. Clofazimine (20 mg/kg) is effective in reducing bacterial loads in the liver, spleen and lungs of C57BL/6 mice experimentally infected with M. avium strain TMC 724. [5]

Protocol

Solubility (25°C)

In vitro DMSO 5 mg/mL (10.56 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 473.4
Formula

C27H22Cl2N4

CAS No. 2030-63-9
Storage powder
Synonyms NSC-141046

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02968212 Not yet recruiting Mycobacterium Avium Complex Oregon Health and Science University|FDA Office of Orphan Products Development|National Heart, Lung, and Blood Institute (NHLBI)|National Jewish Health|The University of Texas Health Science Center at Tyler|National Institute of Allergy and Infectious Diseases (NIAID) April 2017 Phase 2
NCT02589782 Recruiting Tuberculosis, Multidrug-Resistant|Extensively Drug-Resistant Tuberculosis|Tuberculosis, Pulmonary Medecins Sans Frontieres, Netherlands|London School of Hygiene and Tropical Medicine|Global Alliance for TB Drug Development|University College, London|Drugs for Neglected Diseases|Swiss Tropical & Public Health Institute|eResearch Technology, Inc.|Ministry of Health, Republic of Uzbekistan|World Health Organization|Ministry of Health, Belarus|TB & HIV Investigative Network (THINK) January 2017 Phase 2|Phase 3
NCT02754765 Recruiting Tuberculosis, Multidrug-Resistant Médecins Sans Frontières France|Partners in Health|Harvard Medical School|Epicentre|Institute of Tropical Medicine, Belgium|Ministry of Health, Kyrgyzstan|National Center for Tuberculosis Problems, Kazakhstan|Ministry of Health, Lesotho|National Center for Tuberculosis and Lung Diseases, Georgia|Socios En Salud, Peru December 2016 Phase 3
NCT02409290 Recruiting MDR-TB IUATLD, Inc|Medical Research Council April 2016 Phase 3
NCT01691534 Completed Pulmonary Tuberculosis Global Alliance for TB Drug Development October 2012 Phase 2
NCT01290744 Completed Borderline Lepromatous Leprosy|Lepromatous Leprosy Paul Saunderson|Leonard Wood Memorial August 2010 Phase 4

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID