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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:34
Primary Accession Number DB01011
Secondary Accession Number
  • APRD01111
  • EXPT02271
Name Metyrapone
Drug Type
  • Approved
  • Small Molecule
Description An inhibitor of the enzyme steroid 11-beta-monooxygenase. It is used as a test of the feedback hypothalamic-pituitary mechanism in the diagnosis of cushing syndrome. [PubChem]
Synonyms
  1. Mepyrapone
  2. Methapyrapone
  3. Methbipyranone
  4. Methopirapone
  5. Methopyrapone
  6. Methopyrinine
  7. Methopyrone
  8. Metroprione
  9. Metyrapon
Brand Names
  1. Metapirone
  2. Metapyron
  3. Metapyrone
  4. Metopiron
  5. Metopirone
  6. Metopyrone
Brand Mixtures Not Available
Chemical IUPAC Name 2-methyl-1,2-di(pyridin-3-yl)propan-1-one
Chemical Formula C14H14N2O
Chemical Structure Structure
CAS Registry Number 54-36-4
InChI Identifier InChI=1/C14H14N2O/c1-14(2,12-6-4-8-16-10-12)13(17)11-5-3-7-15-9-11/h3-10H,1-2H3
InChI Key FJLBFSROUSIWMA-UHFFFAOYAJ
KEGG Drug D00410 Link Image
KEGG Compound C07205 Link Image
PubChem Compound 4174 Link Image
PubChem Substance 9414 Link Image
ChEBI ID 6911 Link Image
PharmGKB ID PA450486 Link Image
HET ID MYT Link Image
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link http://www.rxlist.com/cgi/generic3/metopirone.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Metyrapone Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 226.2738
Monoisotopic Molecular Weight 226.1106
State Solid
Melting Point 50.5 oC
Experimental Water Solubility Sparingly soluble Source: PhysProp
Predicted Water Solubility 4.27e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 1.8 Source: PhysProp
Predicted LogP 2.09 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.72 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
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 1PHG Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES CC(C)(C(=O)C1=CN=CC=C1)C1=CN=CC=C1
Canonical SMILES CC(C)(C(=O)C1=CN=CC=C1)C1=CN=CC=C1
Drug Category
  • Antimetabolites
  • Enzyme Inhibitors
ATC Codes
AHFS Codes Not Available
Indication Used as a diagnostic drug for testing hypothalamic-pituitary ACTH function.
Pharmacology Metopirone is an inhibitor of endogenous adrenal corticosteroid synthesis.
Mechanism of Action The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the 11-ß-hydroxylation reaction in the adrenal cortex. Removal of the strong inhibitory feedback mechanism exerted by cortisol results in an increase in adrenocorticotropic hormone (ACTH) production by the pituitary. With continued blockade of the enzymatic steps leading to production of cortisol and corticosterone, there is a marked increase in adrenocortical secretion of their immediate precursors, 11-desoxycortisol and desoxycorticosterone, which are weak suppressors of ACTH release, and a corresponding elevation of these steroids in the plasma and of their metabolites in the urine. These metabolites are readily determined by measuring urinary 17-hydroxycorticosteroids (17-OHCS) or 17-ketogenic steroids (17-KGS). Because of these actions, metopirone is used as a diagnostic test, with urinary 17-OHCS measured as an index of pituitary ACTH responsiveness. Metopirone may also suppress biosynthesis of aldosterone, resulting in a mild natriuresis.
Absorption Absorbed rapidly and well when administered orally. Peak plasma concentrations are usually reached 1 hour after administration.
Toxicity Oral LD50 in rats is 521 mg/kg. One case has been recorded in which a 6-year-old girl died after two doses of Metopirone, 2 g. Symptoms of overdose include cardiac arrhythmias, hypotension, dehydration, anxiety, confusion, weakness, impairment of consciousness, nausea, vomiting, epigastric pain, and diarrhea.
Protein Binding Not Available
Biotransformation Hepatic. The major biotransformation is reduction of the ketone to metyrapol, an active alcohol metabolite. Metyrapone and metyrapol are both conjugated with glucuronide.
Half Life 1.9 ±0.7 hours.
Dosage Forms
Form Route
Capsule Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Wikipedia Link Image
  2. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2A6 (CYP2A6)
  2. Cytochrome P450 3A4 (CYP3A4)
  3. Cytochrome P450 11B2 (CYP11B2)
Targets
  1. Cytochrome P450-cam
  2. Cytochrome P450 3A4
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2A6 (CYP2A6)
Enzyme 1 Gene Name CYP2A6
Enzyme 1 SwissProt ID P11509 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P11509|CP2A6_HUMAN Cytochrome P450 2A6 (EC 1.14.14.1) 
MLASGMLLVALLVCLTVMVLMSVWQQRKSKGKLPPGPTPLPFIGNYLQLNTEQMYNSLMK
ISERYGPVFTIHLGPRRVVVLCGHDAVREALVDQAEEFSGRGEQATFDWVFKGYGVVFSN
GERAKQLRRFSIATLRDFGVGKRGIEERIQEEAGFLIDAHRGTGGANIDPTFFLSRTVSN
VISSIVFGDRFDYKDKEFLSLLRMMLGIFQFTSTSTGQLYEMFSSVMKHLPGPQQQAFQL
LQGLEDFIAKKVEHNQRTLDPNSPRDFIDSFLIRMQEEEKNPNTEFYLKNLVMTTLNLFI
GGTETVSTTLRYGFLLLMKHPEVEAKVHEEIDRVIGKNRQPKFEDRAKMPYMEAVIHEIQ
RFGDVIPMSLARRVKKDTKFRDFFLPKGTEVYPMLGSVLRDPSFFSNPQDFNPQHFLNEK
GQFKKSDAFVPFSIGKRNCFGEGLARMELFLFFTTVMQNFRLKSSQSPKDIDVSPKHVGF
ATIPRNYTMSFLPR
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 2 Gene Name CYP3A4
Enzyme 2 SwissProt ID P08684 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Phase 1 Metabolizing Enzyme 3 [top]
Enzyme 3 Name Cytochrome P450 11B2 (CYP11B2)
Enzyme 3 Gene Name CYP11B2
Enzyme 3 SwissProt ID P19099 Link Image
Enzyme 3 SNPs SNPJam Report Link Image
Enzyme 3 Protein Sequence >sp|P19099|C11B2_HUMAN Cytochrome P450 11B2 
MALRAKAEVCVAAPWLSLQRARALGTRAARAPRTVLPFEAMPQHPGNRWLRLLQIWREQG
YEHLHLEMHQTFQELGPIFRYNLGGPRMVCVMLPEDVEKLQQVDSLHPCRMILEPWVAYR
QHRGHKCGVFLLNGPEWRFNRLRLNPDVLSPKAVQRFLPMVDAVARDFSQALKKKVLQNA
RGSLTLDVQPSIFHYTIEASNLALFGERLGLVGHSPSSASLNFLHALEVMFKSTVQLMFM
PRSLSRWISPKVWKEHFEAWDCIFQYGDNCIQKIYQELAFNRPQHYTGIVAELLLKAELS
LEAIKANSMELTAGSVDTTAFPLLMTLFELARNPDVQQILRQESLAAAASISEHPQKATT
ELPLLRAALKETLRLYPVGLFLERVVSSDLVLQNYHIPAGTLVQVFLYSLGRNAALFPRP
ERYNPQRWLDIRGSGRNFHHVPFGFGMRQCLGRRLAEAEMLLLLHHVLKHFLVETLTQED
IKMVYSFILRPGTSPLLTFRAIN
Drug Target 1 [top]
Target 1 ID 2298
Target 1 Name Cytochrome P450-cam
Target 1 Synonyms
  1. Camphor 5-monooxygenase
  2. EC 1.14.15.1
  3. P450cam
Target 1 Gene Name camC
Target 1 Protein Sequence >Cytochrome P450-cam 
MTTETIQSNANLAPLPPHVPEHLVFDFDMYNPSNLSAGVQEAWAVLQESNVPDLVWTRCN
GGHWIATRGQLIREAYEDYRHFSSECPFIPREAGEAYDFIPTSMDPPEQRQFRALANQVV
GMPVVDKLENRIQELACSLIESLRPQGQCNFTEDYAEPFPIRIFMLLAGLPEEDIPHLKY
LTDQMTRPDGSMTFAEAKEALYDYLIPIIEQRRQKPGTDAISIVANGQVNGRPITSDEAK
RMCGLLLVGGLDTVVNFLSFSMEFLAKSPEHRQELIERPERIPAACEELLRRFSLVADGR
ILTSDYEFHGVQLKKGDQILLPQMLSGLDERENACPMHVDFSRQKVSHTTFGHGSHLCLG
QHLARREIIVTLKEWLTRIPDFSIAPGAQIQHKSGIVSGVQALPLVWDPATTKAV
Target 1 Number of Residues 421
Target 1 Molecular Weight 46670
Target 1 Theoretical pI 5.08
Target 1 GO Classification
Function
tetrapyrrole binding
heme binding
binding
ion binding
cation binding
transition metal ion binding
iron ion binding
catalytic activity
oxidoreductase activity
monooxygenase activity
Process
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport
Component
Not Available
Target 1 General Function Secondary metabolites biosynthesis, transport and catabolism
Target 1 Specific Function Involved in a camphor oxidation system
Target 1 Pathways Not Available
Target 1 Reactions
  • (+)-camphor + putidaredoxin + O2 = (+)-exo-5-hydroxycamphor + oxidized putidaredoxin + H2O
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Essential
Target 1 GenBank ID Protein 151115 Link Image
Target 1 UniProtKB/Swiss-Prot ID P00183 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name CPXA_PSEPU Link Image
Target 1 PDB ID 1IWI Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location Not Available
Target 1 Gene Sequence >1248 bp 
ATGACGACTGAAACCATACAAAGCAACGCCAATCTTGCCCCTCTGCCACCCCATGTGCCA
GAGCACCTGGTATTCGACTTCGACATGTACAATCCGTCGAATCTGTCTGCCGGCGTGCAG
GAGGCCTGGGCAGTTCTGCAAGAATCAAACGTACCGGATCTGGTGTGGACTCGCTGCAAC
GGCGGACACTGGATCGCCACTCGCGGCCAACTGATCCGTGAGGCCTATGAAGATTACCGC
CACTTTTCCAGCGAGTGCCCGTTCATCCCTCGTGAAGCCGGCGAAGCCTACGACTTCATT
CCCACCTCGATGGATCCGCCCGAGCAGCGCCAGTTTCGTGCGCTGGCCAACCAAGTGGTT
GGCATGCCGGTGGTGGATAAGCTGGAGAACCGGATCCAGGAGCTGGCCTGCTCGCTGATC
GAGAGCCTGCGCCCGCAAGGACAGTGCAACTTCACCGAGGACTACGCCGAACCCTTCCCG
ATACGCATCTTCATGCTGCTCGCAGGTCTACCGGAAGAAGATATCCCGCACTTGAAATAC
CTAACGGATCAGATGACCCGTCCGGATGGCAGCATGACCTTCGCAGAGGCCAAGGAGGCG
CTCTACGACTATCTGATACCGATCATCGAGCAACGCAGGCAGAAGCCGGGAACCGACGCT
ATCAGCATCGTTGCCAACGGCCAGGTCAATGGGCGACCGATCACCAGTGACGAAGCCAAG
AGGATGTGTGGCCTGTTACTGGTCGGCGGCCTGGATACGGTGGTCAATTTCCTCAGCTTC
AGCATGGAGTTCCTGGCCAAAAGCCCGGAGCATCGCCAGGAGCTGATCGAGCGTCCCGAG
CGTATTCCAGCCGCTTGCGAGGAACTACTCCGGCGCTTCTCGCTGGTTGCCGATGGCCGC
ATCCTCACCTCCGATTACGAGTTTCATGGCGTGCAACTGAAGAAAGGTGACCAGATCCTG
CTACCGCAGATGCTGTCTGGCCTGGATGAGCGCGAAAACGCCTGCCCGATGCACGTCGAC
TTCAGTCGCCAAAAGGTTTCACACACCACCTTTGGCCACGGCAGCCATCTGTGCCTTGGC
CAGCACCTGGCCCGCCGGGAAATCATCGTCACCCTCAAGGAATGGCTGACCAGGATTCCT
GACTTCTCCATTGCCCCGGGTGCCCAGATTCAGCACAAGAGCGGCATCGTCAGCGGCGTG
CAGGCACTCCCTCTGGTCTGGGATCCGGCGACTACCAAAGCGGTATAA
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 SNPJam Report Link Image
Target 1 General References
  1. Dmochowski IJ, Crane BR, Wilker JJ, Winkler JR, Gray HB: Optical detection of cytochrome P450 by sensitizer-linked substrates. Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):12987-90. [PubMed Link Image]
  2. Schlichting I, Berendzen J, Chu K, Stock AM, Maves SA, Benson DE, Sweet RM, Ringe D, Petsko GA, Sligar SG: The catalytic pathway of cytochrome p450cam at atomic resolution. Science. 2000 Mar 3;287(5458):1615-22. [PubMed Link Image]
  3. Hishiki T, Shimada H, Nagano S, Egawa T, Kanamori Y, Makino R, Park SY, Adachi S, Shiro Y, Ishimura Y: X-ray crystal structure and catalytic properties of Thr252Ile mutant of cytochrome P450cam: roles of Thr252 and water in the active center. J Biochem (Tokyo). 2000 Dec;128(6):965-74. [PubMed Link Image]
  4. Lee DS, Park SY, Yamane K, Obayashi E, Hori H, Shiro Y: Structural characterization of n-butyl-isocyanide complexes of cytochromes P450nor and P450cam. Biochemistry. 2001 Mar 6;40(9):2669-77. [PubMed Link Image]
  5. Dunn AR, Dmochowski IJ, Bilwes AM, Gray HB, Crane BR: Probing the open state of cytochrome P450cam with ruthenium-linker substrates. Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12420-5. Epub 2001 Oct 16. [PubMed Link Image]
  6. Deprez E, Gill E, Helms V, Wade RC, Hui Bon Hoa G: Specific and non-specific effects of potassium cations on substrate-protein interactions in cytochromes P450cam and P450lin. J Inorg Biochem. 2002 Sep 20;91(4):597-606. [PubMed Link Image]
  7. Fedorov R, Ghosh DK, Schlichting I: Crystal structures of cyanide complexes of P450cam and the oxygenase domain of inducible nitric oxide synthase-structural models of the short-lived oxygen complexes. Arch Biochem Biophys. 2003 Jan 1;409(1):25-31. [PubMed Link Image]
  8. Nolting B, Jung C, Snatzke G: Multichannel circular dichroism investigations of the structural stability of bacterial cytochrome P-450. Biochim Biophys Acta. 1992 May 20;1100(2):171-6. [PubMed Link Image]
  9. Hui Bon Hoa G, Di Primo C, Dondaine I, Sligar SG, Gunsalus IC, Douzou P: Conformational changes of cytochromes P-450cam and P-450lin induced by high pressure. Biochemistry. 1989 Jan 24;28(2):651-6. [PubMed Link Image]
  10. Koga H, Yamaguchi E, Matsunaga K, Aramaki H, Horiuchi T: Cloning and nucleotide sequences of NADH-putidaredoxin reductase gene (camA) and putidaredoxin gene (camB) involved in cytochrome P-450cam hydroxylase of Pseudomonas putida. J Biochem (Tokyo). 1989 Nov;106(5):831-6. [PubMed Link Image]
  11. 3003058 Unger BP, Gunsalus IC, Sligar SG: Nucleotide sequence of the Pseudomonas putida cytochrome P-450cam gene and its expression in Escherichia coli. J Biol Chem. 1986 Jan 25;261(3):1158-63.
  12. 3813557 Marden MC, Hoa GH: P-450 binding to substrates camphor and linalool versus pressure. Arch Biochem Biophys. 1987 Feb 15;253(1):100-7.
  13. 4066706 Poulos TL, Finzel BC, Gunsalus IC, Wagner GC, Kraut J: The 2.6-A crystal structure of Pseudomonas putida cytochrome P-450. J Biol Chem. 1985 Dec 25;260(30):16122-30.
  14. 7130171 Haniu M, Armes LG, Yasunobu KT, Shastry BA, Gunsalus IC: Amino acid sequence of the Pseudomonas putida cytochrome P-450. II. Cyanogen bromide peptides, acid cleavage peptides, and the complete sequence. J Biol Chem. 1982 Nov 10;257(21):12664-71.
  15. 9315686 Mouro C, Bondon A, Simonneaux G, Jung C: 1H-NMR study of diamagnetic cytochrome P450cam: assignment of heme resonances and substrate dependance of one cysteinate beta proton. FEBS Lett. 1997 Sep 8;414(2):203-8.
  16. 9357977 Schlichting I, Jung C, Schulze H: Crystal structure of cytochrome P-450cam complexed with the (1S)-camphor enantiomer. FEBS Lett. 1997 Oct 6;415(3):253-7.
  17. 9649301 Vidakovic M, Sligar SG, Li H, Poulos TL: Understanding the role of the essential Asp251 in cytochrome p450cam using site-directed mutagenesis, crystallography, and kinetic solvent isotope effect. Biochemistry. 1998 Jun 30;37(26):9211-9.
Target 1 Drug References
  1. Schunemann V, Jung C, Terner J, Trautwein AX, Weiss R: Spectroscopic studies of peroxyacetic acid reaction intermediates of cytochrome P450cam and chloroperoxidase. J Inorg Biochem. 2002 Sep 20;91(4):586-96. [PubMed Link Image]
  2. Bistolas N, Christenson A, Ruzgas T, Jung C, Scheller FW, Wollenberger U: Spectroelectrochemistry of cytochrome P450cam. Biochem Biophys Res Commun. 2004 Feb 13;314(3):810-6. [PubMed Link Image]
  3. 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]
  4. 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]
  5. Shiro Y, Fujii M, Isogai Y, Adachi S, Iizuka T, Obayashi E, Makino R, Nakahara K, Shoun H: Iron-ligand structure and iron redox property of nitric oxide reductase cytochrome P450nor from Fusarium oxysporum: relevance to its NO reduction activity. Biochemistry. 1995 Jul 18;34(28):9052-8. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 4512
Target 2 Name Cytochrome P450 3A4
Target 2 Synonyms
  1. CYPIIIA4
  2. EC 1.14.13.67
  3. EC 1.14.13.97
  4. NF-25
  5. Nifedipine oxidase
  6. P450-PCN1
  7. Quinine 3-monooxygenase
  8. Taurochenodeoxycholate 6-alpha- hydroxylase
Target 2 Gene Name CYP3A4
Target 2 Protein Sequence >Cytochrome P450 3A4 
MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMF
DMECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISI
AEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYS
MDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICV
FPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSI
IFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVV
NETLRLFPIAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHRDPKYWTEPEKFLPERFS
KKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLG
GLLQPEKPVVLKVESRDGTVSGA
Target 2 Number of Residues 511
Target 2 Molecular Weight 57344
Target 2 Theoretical pI 8.25
Target 2 GO Classification
Function
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
tetrapyrrole binding
heme binding
binding
ion binding
cation binding
transition metal ion binding
iron ion binding
catalytic activity
oxidoreductase activity
monooxygenase activity
Process
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport
Component
Not Available
Target 2 General Function Involved in monooxygenase activity
Target 2 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. The enzyme also hydroxylates etoposide
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 2-22
Target 2 Essentiality Non Essential
Target 2 GenBank ID Protein Not Available
Target 2 UniProtKB/Swiss-Prot ID P08684 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name CP3A4_HUMAN Link Image
Target 2 PDB ID 1TQN Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Endoplasmic reticulum
Target 2 Gene Sequence >1512 bp 
ATGGCTCTCATCCCAGACTTGGCCATGGAAACCTGGCTTCTCCTGGCTGTCAGCCTGGTG
CTCCTCTATCTATATGGAACCCATTCACATGGACTTTTTAAGAAGCTTGGAATTCCAGGG
CCCACACCTCTGCCTTTTTTGGGAAATATTTTGTCCTACCATAAGGGCTTTTGTATGTTT
GACATGGAATGTCATAAAAAGTATGGAAAAGTGTGGGGCTTTTATGATGGTCAACAGCCT
GTGCTGGCTATCACAGATCCTGACATGATCAAAACAGTGCTAGTGAAAGAATGTTATTCT
GTCTTCACAAACCGGAGGCCTTTTGGTCCAGTGGGATTTATGAAAAGTGCCATCTCTATA
GCTGAGGATGAAGAATGGAAGAGATTACGATCATTGCTGTCTCCAACCTTCACCAGTGGA
AAACTCAAGGAGATGGTCCCTATCATTGCCCAGTATGGAGATGTGTTGGTGAGAAATCTG
AGGCGGGAAGCAGAGACAGGCAAGCCTGTCACCTTGAAAGACGTCTTTGGGGCCTACAGC
ATGGATGTGATCACTAGCACATCATTTGGAGTGAACATCGACTCTCTCAACAATCCACAA
GACCCCTTTGTGGAAAACACCAAGAAGCTTTTAAGATTTGATTTTTTGGATCCATTCTTT
CTCTCAATAACAGTCTTTCCATTCCTCATCCCAATTCTTGAAGTATTAAATATCTGTGTG
TTTCCAAGAGAAGTTACAAATTTTTTAAGAAAATCTGTAAAAAGGATGAAAGAAAGTCGC
CTCGAAGATACACAAAAGCACCGAGTGGATTTCCTTCAGCTGATGATTGACTCTCAGAAT
TCAAAAGAAACTGAGTCCCACAAAGCTCTGTCCGATCTGGAGCTCGTGGCCCAATCAATT
ATCTTTATTTTTGCTGGCTATGAAACCACGAGCAGTGTTCTCTCCTTCATTATGTATGAA
CTGGCCACTCACCCTGATGTCCAGCAGAAACTGCAGGAGGAAATTGATGCAGTTTTACCC
AATAAGGCACCACCCACCTATGATACTGTGCTACAGATGGAGTATCTTGACATGGTGGTG
AATGAAACGCTCAGATTATTCCCAATTGCTATGAGACTTGAGAGGGTCTGCAAAAAAGAT
GTTGAGATCAATGGGATGTTCATTCCCAAAGGGGTGGTGGTGATGATTCCAAGCTATGCT
CTTCACCGTGACCCAAAGTACTGGACAGAGCCTGAGAAGTTCCTCCCTGAAAGATTCAGC
AAGAAGAACAAGGACAACATAGATCCTTACATATACACACCCTTTGGAAGTGGACCCAGA
AACTGCATTGGCATGAGGTTTGCTCTCATGAACATGAAACTTGCTCTAATCAGAGTCCTT
CAGAACTTCTCCTTCAAACCTTGTAAAGAAACACAGATCCCCCTGAAATTAAGCTTAGGA
GGACTTCTTCAACCAGAAAAACCCGTTGTTCTAAAGGTTGAGTCAAGGGATGGCACCGTA
AGTGGAGCCTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID Not Available
Target 2 GenAtlas ID CYP3A4 Link Image
Target 2 HGNC ID HGNC:2637 Link Image
Target 2 Chromosome Location 7
Target 2 Locus 7q21.1
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Chen Q, Wu J, Yu Y: [Establishment of transgenic cell line CHL-3A4 and its metabolic activation] Zhonghua Yu Fang Yi Xue Za Zhi. 1998 Sep;32(5):281-4. [PubMed Link Image]
  2. Hsieh KP, Lin YY, Cheng CL, Lai ML, Lin MS, Siest JP, Huang JD: Novel mutations of CYP3A4 in Chinese. Drug Metab Dispos. 2001 Mar;29(3):268-73. [PubMed Link Image]
  3. Gellner K, Eiselt R, Hustert E, Arnold H, Koch I, Haberl M, Deglmann CJ, Burk O, Buntefuss D, Escher S, Bishop C, Koebe HG, Brinkmann U, Klenk HP, Kleine K, Meyer UA, Wojnowski L: Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene. Pharmacogenetics. 2001 Mar;11(2):111-21. [PubMed Link Image]
  4. Bork RW, Muto T, Beaune PH, Srivastava PK, Lloyd RS, Guengerich FP: Characterization of mRNA species related to human liver cytochrome P-450 nifedipine oxidase and the regulation of catalytic activity. J Biol Chem. 1989 Jan 15;264(2):910-9. [PubMed Link Image]
  5. Spurr NK, Gough AC, Stevenson K, Wolf CR: The human cytochrome P450 CYP3 locus: assignment to chromosome 7q22-qter. Hum Genet. 1989 Jan;81(2):171-4. [PubMed Link Image]
  6. Komori M, Hashizume T, Ohi H, Miura T, Kitada M, Nagashima K, Kamataki T: Cytochrome P-450 in human liver microsomes: high-performance liquid chromatographic isolation of three forms and their characterization. J Biochem. 1988 Dec;104(6):912-6. [PubMed Link Image]
  7. Gonzalez FJ, Schmid BJ, Umeno M, Mcbride OW, Hardwick JP, Meyer UA, Gelboin HV, Idle JR: Human P450PCN1: sequence, chromosome localization, and direct evidence through cDNA expression that P450PCN1 is nifedipine oxidase. DNA. 1988 Mar;7(2):79-86. [PubMed Link Image]
  8. Beaune PH, Umbenhauer DR, Bork RW, Lloyd RS, Guengerich FP: Isolation and sequence determination of a cDNA clone related to human cytochrome P-450 nifedipine oxidase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8064-8. [PubMed Link Image]
  9. Zhang H, Coville PF, Walker RJ, Miners JO, Birkett DJ, Wanwimolruk S: Evidence for involvement of human CYP3A in the 3-hydroxylation of quinine. Br J Clin Pharmacol. 1997 Mar;43(3):245-52. [PubMed Link Image]
Target 2 Drug References Not Available

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.