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Record Information
Version2.0
Creation Date2009-07-21 20:27:15 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2838
Identification
Common NameRifabutin
ClassSmall Molecule
DescriptionRifabutin is only found in individuals that have used or taken this drug. It is a broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients. [PubChem]Rifabutin acts via the inhibition of DNA-dependent RNA polymerase in gram-positive and some gram-negative bacteria, leading to a suppression of RNA synthesis and cell death.
Compound Type
  • Amide
  • Amine
  • Anti-Bacterial Agent
  • Antibiotic, Antitubercular
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
4-Deoxo-3,4-(2-spiro(N-isobutyl-4-piperidyl)-2,5-dihydro-1H-imidazo)-rifamycin S
4-N-Isobutylspiropiperidylrifamycin S
Ansamicin
Ansamycin
Ansatipin
Ansatipine
Antibiotic LM 427
Mycobutin
RBT
Ributin
Rifabutina
Rifabutine
Rifabutinum
Chemical FormulaC46H62N4O11
Average Molecular Mass847.005 g/mol
Monoisotopic Mass846.442 g/mol
CAS Registry Number72559-06-9
IUPAC Name(7S,9Z,11S,12R,13S,14R,15R,16R,17S,18S,19Z,21Z)-2,15,17,23-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-1'-(2-methylpropyl)-6,32-dioxo-8,33-dioxa-24,27,29-triazaspiro[pentacyclo[23.6.1.1^{4,7}.0^{5,31}.0^{26,30}]tritriacontane-28,4'-piperidine]-1(31),2,4,9,19,21,23,25,29-nonaen-13-yl acetate
Traditional Name(7S,9Z,11S,12R,13S,14R,15R,16R,17S,18S,19Z,21Z)-2,15,17,23-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-1'-(2-methylpropyl)-6,32-dioxo-8,33-dioxa-24,27,29-triazaspiro[pentacyclo[23.6.1.1^{4,7}.0^{5,31}.0^{26,30}]tritriacontane-28,4'-piperidine]-1(31),2,4,9,19,21,23,25,29-nonaen-13-yl acetate
SMILES[H]\C1=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)=NC2=C3NC4(CCN(CC(C)C)CC4)N=C3C3=C(C(O)=C(C)C4=C3C(=O)[C@](C)(O4)O1)C2=O
InChI IdentifierInChI=1S/C46H62N4O11/c1-22(2)21-50-18-16-46(17-19-50)48-34-31-32-39(54)28(8)42-33(31)43(56)45(10,61-42)59-20-15-30(58-11)25(5)41(60-29(9)51)27(7)38(53)26(6)37(52)23(3)13-12-14-24(4)44(57)47-36(40(32)55)35(34)49-46/h12-15,20,22-23,25-27,30,37-38,41,49,52-54H,16-19,21H2,1-11H3,(H,47,57)/b13-12-,20-15-,24-14-/t23-,25+,26+,27+,30-,37-,38+,41+,45-/m0/s1
InChI KeyInChIKey=ATEBXHFBFRCZMA-DVAZEERGSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as macrolactams. These are cyclic amides of amino carboxylic acids, having a 1-azacycloalkan-2-one structure, or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. They are nitrogen analogues (the a nitrogen atom replacing the o atom of the cyclic carboxylic acid group ) of the naturally occurring macrolides.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassMacrolactams
Sub ClassNot Available
Direct ParentMacrolactams
Alternative Parents
Substituents
  • Naphthofuran
  • Macrolactam
  • Azaspirodecane
  • Naphthalene
  • Benzofuran
  • Coumaran
  • Aryl ketone
  • Aryl alkyl ketone
  • Ketal
  • Piperidine
  • Benzenoid
  • 3-imidazoline
  • Vinylogous amide
  • Vinylogous acid
  • Lactam
  • Ketimine
  • Amino acid or derivatives
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxylic acid ester
  • Ketone
  • Carboxamide group
  • Secondary alcohol
  • Acetal
  • Carboxylic acid derivative
  • Dialkyl ether
  • Secondary aliphatic amine
  • Enamine
  • Ether
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Monocarboxylic acid or derivatives
  • Polyol
  • Secondary amine
  • Organic oxygen compound
  • Organopnictogen compound
  • Imine
  • Carbonyl group
  • Organic oxide
  • Alcohol
  • Hydrocarbon derivative
  • Amine
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
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 RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityMinimally soluble (0.19 mg/mL)
LogP4.1
Predicted Properties
PropertyValueSource
Water Solubility0.0091 g/LALOGPS
logP4.31ALOGPS
logP3.44ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)5.29ChemAxon
pKa (Strongest Basic)7.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area209.04 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity233.17 m³·mol⁻¹ChemAxon
Polarizability91.1 ųChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-06vi-2000000290-b6c2e05a4e08c21c8009JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-8000002970-8db040b5d2c5d1c7f870JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000003500-61568975d849f4e01490JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-1000000390-013052b1c69581676709JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0kbs-2000000790-222783e8f7fc477df855JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000m-3000001910-593444223c16d943f93eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-05pa-0000000970-2dfaa272c475120f1997JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00kr-0000000930-3f004468a35f4bfc7d81JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00kk-0000000950-e0fa551433e76d0694bbJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-1000000290-6b79ec41174e5c65892fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-6000000930-138088289c4e164844b3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000l-2000000940-3d9bc441c2d70d547151JSpectraViewer
Toxicity Profile
Route of ExposureRifabutin is readily absorbed from the gastrointestinal tract, with an absolute bioavailability averaging 20%.
Mechanism of ToxicityRifabutin acts via the inhibition of DNA-dependent RNA polymerase in gram-positive and some gram-negative bacteria, leading to a suppression of RNA synthesis and cell death.
MetabolismHepatic. Of the five metabolites that have been identified, 25-O-desacetyl and 31-hydroxy are the most predominant. The former metabolite has an activity equal to the parent drug and contributes up to 10% to the total antimicrobial activity. Route of Elimination: A mass-balance study in three healthy adult volunteers with 14C-labeled rifabutin showed that 53% of the oral dose was excreted in the urine, primarily as metabolites. About 30% of the dose is excreted in the feces. Half Life: 45 (± 17) hours
Toxicity ValuesLD50: 4.8 g/kg (male mouse)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the prevention of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection. Used in the treatment of tuberculosis. It has also found to be useful in the treatment of (Chlamydia) Chlamydophila pneumoniae (Cpn) Infection.[Wikipedia]
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms include diarrhea, eructation, abdominal pain, vomitting, nausea, and insomnia.
TreatmentClinical experience with rifamycins suggests that gastric lavage to evacuate gastric contents (within a few hours of overdose), followed by instillation of an activated charcoal slurry into the stomach, may help absorb any remaining drug from the gastrointestinal tract. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00615
HMDB IDHMDB14753
PubChem Compound ID6323490
ChEMBL IDCHEMBL444633
ChemSpider ID4883445
KEGG IDC07235
UniProt IDNot Available
OMIM ID
ChEBI ID8857
BioCyc IDNot Available
CTD IDNot Available
Stitch IDRifabutin
PDB IDRBT
ACToR IDNot Available
Wikipedia LinkRifabutin
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Drugs.com [Link]
  2. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

General Function:
Tpr domain binding
Specific Function:
Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes.
Gene Name:
HSP90AA1
Uniprot ID:
P07900
Molecular Weight:
84659.015 Da
References
  1. Schnaider T, Somogyi J, Csermely P, Szamel M: The Hsp90-specific inhibitor geldanamycin selectively disrupts kinase-mediated signaling events of T-lymphocyte activation. Cell Stress Chaperones. 2000 Jan;5(1):52-61. [10701840 ]
  2. Neckers L, Schulte TW, Mimnaugh E: Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity. Invest New Drugs. 1999;17(4):361-73. [10759403 ]
  3. Srethapakdi M, Liu F, Tavorath R, Rosen N: Inhibition of Hsp90 function by ansamycins causes retinoblastoma gene product-dependent G1 arrest. Cancer Res. 2000 Jul 15;60(14):3940-6. [10919672 ]
  4. Munster PN, Srethapakdi M, Moasser MM, Rosen N: Inhibition of heat shock protein 90 function by ansamycins causes the morphological and functional differentiation of breast cancer cells. Cancer Res. 2001 Apr 1;61(7):2945-52. [11306472 ]
  5. Yang J, Yang JM, Iannone M, Shih WJ, Lin Y, Hait WN: Disruption of the EF-2 kinase/Hsp90 protein complex: a possible mechanism to inhibit glioblastoma by geldanamycin. Cancer Res. 2001 May 15;61(10):4010-6. [11358819 ]
General Function:
Virion binding
Specific Function:
Molecular chaperone that functions in the processing and transport of secreted proteins. When associated with CNPY3, required for proper folding of Toll-like receptors (By similarity). Functions in endoplasmic reticulum associated degradation (ERAD). Has ATPase activity.
Gene Name:
HSP90B1
Uniprot ID:
P14625
Molecular Weight:
92468.06 Da
References
  1. Barzilay E, Ben-Califa N, Supino-Rosin L, Kashman Y, Hirschberg K, Elazar Z, Neumann D: Geldanamycin-associated inhibition of intracellular trafficking is attributed to a co-purified activity. J Biol Chem. 2004 Feb 20;279(8):6847-52. Epub 2003 Dec 1. [14660597 ]
  2. Chavany C, Mimnaugh E, Miller P, Bitton R, Nguyen P, Trepel J, Whitesell L, Schnur R, Moyer J, Neckers L: p185erbB2 binds to GRP94 in vivo. Dissociation of the p185erbB2/GRP94 heterocomplex by benzoquinone ansamycins precedes depletion of p185erbB2. J Biol Chem. 1996 Mar 1;271(9):4974-7. [8617772 ]
  3. Lawson B, Brewer JW, Hendershot LM: Geldanamycin, an hsp90/GRP94-binding drug, induces increased transcription of endoplasmic reticulum (ER) chaperones via the ER stress pathway. J Cell Physiol. 1998 Feb;174(2):170-8. [9428803 ]