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Record Information
Version2.0
Creation Date2009-07-21 20:28:15 UTC
Update Date2014-12-24 20:25:54 UTC
Accession NumberT3D2969
Identification
Common NameRifampin
ClassSmall Molecule
DescriptionA semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)
Compound Type
  • Amide
  • Amine
  • Antibiotic
  • Antibiotic, Antitubercular
  • Antitubercular Agent
  • Antituberculosis Agent
  • Drug
  • Enzyme Inhibitor
  • Ester
  • Ether
  • Hydrazine
  • Leprostatic Agent
  • Metabolite
  • Nucleic Acid Synthesis Inhibitor
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
3-(((4-Methyl-1-piperazinyl)imino)methyl)rifamycin sv
RFP
Rifadin
Rifadine
Rifaldin
Rifampicin
Rifampicina
Rifampicinum
Rifoldin
Rimactan
Rimactane
Rofact
Tubocin
Chemical FormulaC43H58N4O12
Average Molecular Mass822.940 g/mol
Monoisotopic Mass822.405 g/mol
CAS Registry Number13292-46-1
IUPAC Name(7S,9Z,11S,12R,13S,14R,15R,16R,17S,18S,21Z)-2,15,17,23,27,29-hexahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-26-{[(4-methylpiperazin-1-yl)imino]methyl}-6-oxo-8,30-dioxa-24-azatetracyclo[23.3.1.1^{4,7}.0^{5,28}]triaconta-1(28),2,4,9,19,21,23,25(29),26-nonaen-13-yl acetate
Traditional Name(7S,9Z,11S,12R,13S,14R,15R,16R,17S,18S,21Z)-2,15,17,23,27,29-hexahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-26-{[(4-methylpiperazin-1-yl)imino]methyl}-6-oxo-8,30-dioxa-24-azatetracyclo[23.3.1.1^{4,7}.0^{5,28}]triaconta-1(28),2,4,9,19,21,23,25(29),26-nonaen-13-yl acetate
SMILES[H]C(=NN1CCN(C)CC1)C1=C(O)C2=C3C(O)=C(C)C4=C2C(=O)[C@](C)(O4)O\C([H])=C([H])/[C@]([H])(OC)[C@@]([H])(C)[C@@]([H])(OC(C)=O)[C@]([H])(C)[C@]([H])(O)[C@]([H])(C)[C@@]([H])(O)[C@@]([H])(C)C([H])=C([H])\C([H])=C(C)/C(O)=NC1=C3O
InChI IdentifierInChI=1S/C43H58N4O12/c1-21-12-11-13-22(2)42(55)45-33-28(20-44-47-17-15-46(9)16-18-47)37(52)30-31(38(33)53)36(51)26(6)40-32(30)41(54)43(8,59-40)57-19-14-29(56-10)23(3)39(58-27(7)48)25(5)35(50)24(4)34(21)49/h11-14,19-21,23-25,29,34-35,39,49-53H,15-18H2,1-10H3,(H,45,55)/b12-11+,19-14-,22-13-,44-20-/t21-,23+,24+,25+,29-,34-,35+,39+,43-/m0/s1
InChI KeyInChIKey=JQXXHWHPUNPDRT-XHVADFQNSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as naphthofurans. Naphthofurans are compounds containing a furan ring fused to a naphthalene moiety. Furan is a 5 membered- ring aromatic ring with four carbon and one oxygen atoms. Naphthalene is a polycyclic aromatic hydrocarbon made up of two fused benzene rings.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthofurans
Sub ClassNot Available
Direct ParentNaphthofurans
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point183°C
Boiling PointNot Available
Solubility1400 mg/L (at 25°C)
LogP2.7
Predicted Properties
PropertyValueSource
Water Solubility0.025 g/LALOGPS
logP3.91ALOGPS
logP3.22ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)-1.6ChemAxon
pKa (Strongest Basic)15.13ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count15ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area223.64 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity226.34 m³·mol⁻¹ChemAxon
Polarizability86.02 ųChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_6) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-08fr-0500000980-bcda18a9b24d3d79bd0fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-06re-2000002920-94cf3ba1024f60e0d138JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05fu-9100004200-9e06a013254c65e92b1bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-3000001890-0f3bb09775c02b839efdJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-08fr-6400004940-8b7df11383262cc72600JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a7l-9000006400-07b6061e661dceef4411JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-05fs-0000000980-cb73939dde5e32bb8f04JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-08mj-0000000920-d46bb707a0a349fd5104JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0aor-9000001720-cfb21aab6c00cbf1cebaJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-1000001970-fb31d2ee3ab42795a510JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-9000000000-c78a5fe9b5c2c64d82b7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0aba-6100009620-791625018751337a6228JSpectraViewer
Toxicity Profile
Route of ExposureOral. Well absorbed from gastrointestinal tract.
Mechanism of ToxicityRifampin acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.
MetabolismPrimarily hepatic, rapidly deacetylated. Route of Elimination: Less than 30% of the dose is excreted in the urine as rifampin or metabolites. Half Life: 3.35 (+/- 0.66) hours
Toxicity ValuesLD50: 1570 mg/kg (Rat) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (5)
Uses/SourcesFor the treatment of Tuberculosis and Tuberculosis-related mycobacterial infections.
Minimum Risk LevelNot Available
Health EffectsAntibiotic resistance
SymptomsChronic exposure may cause nausea and vomiting and unconsciousness
TreatmentIntensive support measures should be instituted and individual symptoms treated as they arise. Since nausea and vomiting are likely to be present, gastric lavage is probably preferable to induction of emesis. Following evacuation of the gastric contents, the instillation of activated charcoal slurry into the stomach may help absorb any remaining drug from the gastrointestinal tract. Antiemetic medication may be required to control severe nausea and vomiting. Active diuresis (with measured intake and output) will help promote excretion of the drug. Hemodialysis may be of value in some patients. (4)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01045
HMDB IDHMDB15179
PubChem Compound ID5381226
ChEMBL IDCHEMBL374478
ChemSpider ID10468813
KEGG IDC06688
UniProt IDNot Available
OMIM ID
ChEBI ID28077
BioCyc IDNot Available
CTD IDNot Available
Stitch IDRifampin
PDB IDRFP
ACToR IDNot Available
Wikipedia LinkRifampin
References
Synthesis Reference

Klaus Jurgen, Joachim Seydel, “Combination preparations containing rifampicin and thioacetazon.” U.S. Patent US5104875, issued August, 1973.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Baysarowich J, Koteva K, Hughes DW, Ejim L, Griffiths E, Zhang K, Junop M, Wright GD: Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr. Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4886-91. doi: 10.1073/pnas.0711939105. Epub 2008 Mar 18. [18349144 ]
  3. Drugs.com [Link]
  4. RxList: The Internet Drug Index (2009). [Link]
  5. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.85 uMATG_PXRE_CISAttagene
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Harmsen S, Meijerman I, Febus CL, Maas-Bakker RF, Beijnen JH, Schellens JH: PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon adenocarcinoma-derived cell line. Cancer Chemother Pharmacol. 2010 Sep;66(4):765-71. doi: 10.1007/s00280-009-1221-4. Epub 2009 Dec 30. [20041327 ]
  3. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Kuypers DR, Verleden G, Naesens M, Vanrenterghem Y: Drug interaction between mycophenolate mofetil and rifampin: possible induction of uridine diphosphate-glucuronosyltransferase. Clin Pharmacol Ther. 2005 Jul;78(1):81-8. [16003296 ]
  2. Gurley BJ, Barone GW, Williams DK, Carrier J, Breen P, Yates CR, Song PF, Hubbard MA, Tong Y, Cheboyina S: Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos. 2006 Jan;34(1):69-74. Epub 2005 Oct 12. [16221754 ]
  3. Chen J, Raymond K: Roles of rifampicin in drug-drug interactions: underlying molecular mechanisms involving the nuclear pregnane X receptor. Ann Clin Microbiol Antimicrob. 2006 Feb 15;5:3. [16480505 ]
  4. Lamba J, Strom S, Venkataramanan R, Thummel KE, Lin YS, Liu W, Cheng C, Lamba V, Watkins PB, Schuetz E: MDR1 genotype is associated with hepatic cytochrome P450 3A4 basal and induction phenotype. Clin Pharmacol Ther. 2006 Apr;79(4):325-38. Epub 2006 Feb 20. [16580901 ]
  5. Huang R, Murry DJ, Kolwankar D, Hall SD, Foster DR: Vincristine transcriptional regulation of efflux drug transporters in carcinoma cell lines. Biochem Pharmacol. 2006 Jun 14;71(12):1695-704. Epub 2006 Apr 18. [16620787 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory1.1 uMNot AvailableBindingDB 50370232
Inhibitory17 uMNot AvailableBindingDB 50370232
IC501.2 uMNot AvailableBindingDB 50370232
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [22541068 ]
  2. Vavricka SR, Van Montfoort J, Ha HR, Meier PJ, Fattinger K: Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver. Hepatology. 2002 Jul;36(1):164-72. [12085361 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B3
Uniprot ID:
Q9NPD5
Molecular Weight:
77402.175 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory1.4 uMNot AvailableBindingDB 50370232
Inhibitory5 uMNot AvailableBindingDB 50370232
IC501.5 uMNot AvailableBindingDB 50370232
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [22541068 ]
  2. Vavricka SR, Van Montfoort J, Ha HR, Meier PJ, Fattinger K: Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver. Hepatology. 2002 Jul;36(1):164-72. [12085361 ]
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Paul KB, Thompson JT, Simmons SO, Vanden Heuvel JP, Crofton KM: Evidence for triclosan-induced activation of human and rodent xenobiotic nuclear receptors. Toxicol In Vitro. 2013 Oct;27(7):2049-60. doi: 10.1016/j.tiv.2013.07.008. Epub 2013 Jul 27. [23899473 ]
General Function:
Sterol 14-demethylase activity
Specific Function:
Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Gene Name:
CYP51A1
Uniprot ID:
Q16850
Molecular Weight:
56805.26 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5030 uMNot AvailableBindingDB 50370232
References
  1. Ekins S, Mankowski DC, Hoover DJ, Lawton MP, Treadway JL, Harwood HJ Jr: Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitors. Drug Metab Dispos. 2007 Mar;35(3):493-500. Epub 2006 Dec 28. [17194716 ]
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation12 uMNot AvailableBindingDB 50370232
References
  1. Baneres-Roquet F, Gualtieri M, Villain-Guillot P, Pugniere M, Leonetti JP: Use of a surface plasmon resonance method to investigate antibiotic and plasma protein interactions. Antimicrob Agents Chemother. 2009 Apr;53(4):1528-31. doi: 10.1128/AAC.00971-08. Epub 2009 Jan 21. [19164148 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibited by the grapefruit juice component naringin.
Gene Name:
SLCO1A2
Uniprot ID:
P46721
Molecular Weight:
74144.105 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory51 uMNot AvailableBindingDB 50370232
References
  1. Vavricka SR, Van Montfoort J, Ha HR, Meier PJ, Fattinger K: Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver. Hepatology. 2002 Jul;36(1):164-72. [12085361 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name:
SLCO2B1
Uniprot ID:
O94956
Molecular Weight:
76709.98 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory63 uMNot AvailableBindingDB 50370232
IC5065 uMNot AvailableBindingDB 50370232
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [22541068 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC505.80 uMNVS_ADME_hCYP2C9Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]