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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:07:32
Primary Accession Number DB00845
Secondary Accession Number
  • APRD00278
Name Clofazimine
Drug Type
  • Approved
  • Small Molecule
Description A fat-soluble riminophenazine dye used for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum. (From AMA Drug Evaluations Annual, 1993, p1619)
Synonyms
  1. Chlofazimine
  2. Clofazimina [INN-Spanish]
  3. Clofaziminum [INN-Latin]
Brand Names
  1. Lampren
  2. Lamprene
Brand Mixtures Not Available
Chemical IUPAC Name N,5-bis(4-chlorophenyl)-3-propan-2-yliminophenazin-2-amine
Chemical Formula C27H22Cl2N4
Chemical Structure Structure
CAS Registry Number 2030-63-9
InChI Identifier InChI=1/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/b30-24+
InChI Key WDQPAMHFFCXSNU-BGABXYSRBX
KEGG Drug D00278 Link Image
KEGG Compound C06915 Link Image
PubChem Compound 2794 Link Image
PubChem Substance 159498 Link Image
ChEBI ID Not Available
PharmGKB ID PA449044 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link http://www.rxlist.com/cgi/generic3/clofazimine.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Clofazimine Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 473.3960
Monoisotopic Molecular Weight 472.1222
State Solid
Melting Point 210-212 oC
Experimental Water Solubility 0.225 mg/L (virtually insoluble) Source: PhysProp
Predicted Water Solubility 1.51e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 7 Source: PhysProp
Predicted LogP 7.39 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -5.50 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 8.51
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CC(C)\N=C1/C=C2N(C3=CC=C(Cl)C=C3)C3=CC=CC=C3N=C2C=C/1NC1=CC=C(Cl)C=C1
Canonical SMILES CC(C)N=C1C=C2N(C3=CC=C(Cl)C=C3)C3=CC=CC=C3N=C2C=C1NC1=CC=C(Cl)C=C1
Drug Category
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antimycobacterials
  • Coloring Agents
  • Dyes
  • Leprostatic Agents
ATC Codes
AHFS Codes Not Available
Indication For the treatment of lepromatous leprosy, including dapsone-resistant lepromatous leprosy and lepromatous leprosy complicated by erythema nodosum leprosum.
Pharmacology Clofazimine exerts a slow bactericidal effect on Mycobacterium leprae (Hansen's bacillus). Clofazimine inhibits mycobacterial growth and binds preferentially to mycobacterial DNA. Clofazimine also exerts antiinflammatory properties in controlling erythema nodosum leprosum reactions. Clofazimine is highly lipophilic and tends to be deposited predominantly in fatty tissue and in cells of the reticuloendothelial system. It is taken up by macrophages throughout the body. Measurement of the minimum inhibitory concentration (MIC) of clofazimine against leprosy bacilli in vitro is not yet feasible. In the mouse footpad system, the multiplication of M.leprae is inhibited by introducing 0.0001%- 0.001% clofazimine in the diet. Although bacterial killing may begin shortly after starting the drug, it cannot be measured in biopsy tissues taken from patients for mouse footpad studies until approximately 50 days after the start of therapy.
Mechanism of Action Appears to preferentially bind to mycobacterial DNA leading to disruption of the cell cycle and eventually kills the bacterium. It may also bind to bacterial potassium transporters, thereby inhibiting their function. Lysophospholipids have been found to mediate the activity of this drug.
Absorption Absorption varies from 45 to 62% following oral administration in leprosy patients. Bioavailability is approximately 70%. Food increases bioavailability and rate of absorption.
Toxicity Oral, rabbit: LD50 = 3.3 g/kg; Oral, mouse: LD50 = > 4 g/kg. Severe abdominal symptoms have necessitated exploratory laparotomies in some patients on clofazimine therapy. Rare reports have included splenic infarction, bowel obstruction, and gastrointestinal bleeding. Deaths have been reported, following severe abdominal symptoms.
Protein Binding Not Available
Biotransformation Hepatic. Three metabolites have been identified - two conjugated and one unconjugated, however, it is not yet known whether these metabolites are pharmacologically active. Metabolite I is formed by hydrolytic dehalogenation of clofazimine, metabolite II presumably is formed by a hydrolytic deamination reaction followed by glucuronidation, and metabolite III appears to be a hydrated clofazimine glucuronide.
Half Life 10 days following a single dose, 70 days after long-term, high-dose therapy.
Dosage Forms
Form Route
Capsule Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Mycobacteria
Targets
  1. Potassium transporter
  2. DNA
Drug Target 1 [top]
Target 1 ID 683
Target 1 Name Potassium transporter
Target 1 Synonyms
  1. Trk family
Target 1 Gene Name Not Available
Target 1 Protein Sequence >Potassium transporter 
MQHIVDVLVIGASQAGLAMGYYLKQNNILFAIVGKENRIGDVWRNRYDSLVLFTPRWFSS
LPGMALKGDPNGYPTKDEIADYLEDYAQKFELPIHLNTEVISLQKEDEIFKVTTNNGNYV
AEKVVVATGPFQKPYIPPFAESLSDKVYQVHTSRYLNPSQLQEGSVLVVGAGNSGAQIAV
ELSEDREVYLSVGHKMKFFPLEIMGKSIFWWFKKLGLLNVHINSSLGQFISKQSDPIFGK
ELKHLIQEGKIKIKPRTESILGDVISFADNSQIQVQNVIWATGFYSDYSWIQIPNVLDHR
GKPIHQRGVTSVKGLYFLGLPWQYRRGSALIGGVGADAEYLINDILNH
Target 1 Number of Residues 353
Target 1 Molecular Weight 39137
Target 1 Theoretical pI 7.37
Target 1 GO Classification
Function
catalytic activity
oxidoreductase activity
Process
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport
Component
Not Available
Target 1 General Function Inorganic ion transport and metabolism
Target 1 Specific Function Not Available
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Essential
Target 1 GenBank ID Protein 56378959 Link Image
Target 1 UniProtKB/Swiss-Prot ID Q5L2G3 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name Q5L2G3_GEOKA Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location Not Available
Target 1 Gene Sequence >1047 bp 
ATGCAACACATCGTTGATGTTCTGGTTATCGGTGCTAGTCAGGCAGGACTAGCGATGGGA
TATTATCTGAAACAAAATAATATATTGTTTGCCATTGTTGGCAAGGAAAATCGAATCGGA
GATGTTTGGAGAAACCGATATGATTCCTTAGTTCTTTTTACTCCTCGCTGGTTCAGTTCT
TTGCCAGGAATGGCTTTAAAGGGTGACCCGAACGGATATCCAACCAAGGATGAAATTGCC
GATTATTTAGAGGATTATGCTCAAAAATTTGAATTACCTATTCATCTGAACACAGAAGTC
ATTTCCCTTCAAAAAGAAGATGAGATTTTTAAAGTTACAACCAATAATGGTAATTATGTG
GCAGAGAAAGTGGTTGTAGCAACGGGTCCTTTCCAAAAGCCATACATTCCACCATTTGCA
GAAAGCTTATCCGATAAAGTGTATCAAGTGCATACATCCCGTTATTTGAATCCATCTCAA
TTACAAGAAGGCTCTGTTTTGGTAGTCGGTGCGGGAAATTCAGGGGCACAAATTGCTGTT
GAATTGTCCGAAGACAGAGAAGTTTATTTATCTGTAGGTCATAAAATGAAGTTCTTTCCA
CTTGAAATAATGGGTAAAAGTATTTTCTGGTGGTTTAAAAAATTAGGTTTATTAAATGTC
CATATCAACAGCTCGTTAGGTCAGTTTATCAGTAAGCAAAGTGACCCTATTTTCGGTAAA
GAACTGAAACATTTAATACAAGAAGGCAAAATTAAAATTAAACCCAGAACAGAAAGTATT
TTAGGAGATGTTATTTCTTTTGCAGATAACAGTCAAATTCAAGTTCAAAATGTCATTTGG
GCAACTGGATTTTATTCTGATTACAGTTGGATTCAAATTCCGAATGTTTTAGACCATAGA
GGAAAGCCCATTCACCAAAGAGGGGTAACTTCTGTGAAAGGATTGTACTTCTTGGGATTG
CCGTGGCAGTATCGAAGGGGATCTGCTCTTATTGGAGGAGTGGGTGCCGATGCAGAGTAT
TTGATAAATGATATTTTAAACCATTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID Not Available
Target 1 HGNC ID Not Available
Target 1 Chromosome Location Not Available
Target 1 Locus Not Available
Target 1 SNPs Not Available
Target 1 General References Not Available
Target 1 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 874
Target 2 Name DNA
Target 2 Synonyms
  1. Deoxyribonucleic acid
Target 2 Gene Name Not Available
Target 2 Protein Sequence Not Available
Target 2 Number of Residues 0
Target 2 Molecular Weight 7656 (double strand)
Target 2 Theoretical pI Not Available
Target 2 GO Classification
Function
information storage
information transfer
Process
DNA replication and chromosomal cycle
DNA replication
DNA-dependent DNA replication
DNA replication, synthesis of RNA primer
transcription
transcription, DNA dependent
Component
cell
intracellular
nucleus
mitochondria
Target 2 General Function Biological information storage and information transfer
Target 2 Specific Function DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
Target 2 Pathways
Name SMPDB Link KEGG Link
DNA polymerase map03030 Link Image
RNA polymerase map03020 Link Image
Target 2 Reactions
  • DNA + DNA polymerase + nNTP = 2 DNA + nNDP; DNA + RNA polymerase + NTP = mRNA + nNDP
Target 2 Pfam Domain Function Not Available
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Essential
Target 2 GenBank ID Protein Not Available
Target 2 UniProtKB/Swiss-Prot ID Not Available
Target 2 UniProtKB/Swiss-Prot Entry Name Not Available
Target 2 PDB ID 1BNA Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Nucleus and mitochondria
Target 2 Gene Sequence >Example: Dickerson dodecamer 
CGCGAATTCGCG
Target 2 GenBank Gene ID
Target 2 GeneCard ID Not Available
Target 2 GenAtlas ID Not Available
Target 2 HGNC ID Not Available
Target 2 Chromosome Location Not Available
Target 2 Locus All loci
Target 2 SNPs Not Available
Target 2 General References
  1. Nadeau D, Marchand C: Change in the kinetics of sulphacetamide tissue distribution in Walker tumor-bearing rats. Drug Metab Dispos. 1975 Nov-Dec;3(6):565-76. [PubMed Link Image]
Target 2 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.