Target Information
Target General Information | Top | |||||
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Target ID |
T57392
(Former ID: TTDS00475)
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Target Name |
Debrisoquine 4-hydroxylase (CYP2D6)
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Synonyms |
P450-DB1; Cytochrome P450-DB1; Cytochrome P450 2D6; CYPIID6; CYP2DL1
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Gene Name |
CYP2D6
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Insomnia [ICD-11: 7A00-7A0Z] | |||||
Function |
It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants. Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes.
Click to Show/Hide
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BioChemical Class |
Paired donor oxygen oxidoreductase
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UniProt ID | ||||||
EC Number |
EC 1.14.14.-
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Sequence |
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI HEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV FAFLVSPSPYELCAVPR Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
ADReCS ID | BADD_A00232 ; BADD_A00323 ; BADD_A00378 ; BADD_A01205 ; BADD_A01334 ; BADD_A01338 ; BADD_A01965 ; BADD_A01976 ; BADD_A02053 ; BADD_A02189 ; BADD_A02978 ; BADD_A03487 ; BADD_A03957 ; BADD_A04155 ; BADD_A04234 ; BADD_A04424 ; BADD_A05280 ; BADD_A05962 ; BADD_A06157 ; BADD_A06627 | |||||
HIT2.0 ID | T11ZYR |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | Glutethimide | Drug Info | Approved | Insomnia | [2], [3] | |
Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | ISOQUINE | Drug Info | Phase 1 | Malaria | [4] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inducer | [+] 1 Inducer drugs | + | ||||
1 | Glutethimide | Drug Info | [1], [5] | |||
Inhibitor | [+] 46 Inhibitor drugs | + | ||||
1 | ISOQUINE | Drug Info | [6] | |||
2 | (2-hydroxy-3-phenoxypropyl)(propan-2-yl)amine | Drug Info | [7] | |||
3 | (5-(pyridin-3-yl)furan-2-yl)methanamine | Drug Info | [8] | |||
4 | (5-phenylfuran-2-yl)methanamine | Drug Info | [8] | |||
5 | (5-pyridin-3-yl-furan-2-yl)methanethiol | Drug Info | [8] | |||
6 | 1,5-bis(4-hydroxyphenyl)penta-1,4-dien-3-one | Drug Info | [9] | |||
7 | 1-(3,4-DICHLOROPHENYL)-6-(METHOXYMETHYL)-3-AZABICYCLO[4.1.0]HEPTANE (ENANTIOMERIC MIX) | Drug Info | [10] | |||
8 | 1-(4-Butoxy-phenyl)-1H-imidazole | Drug Info | [11] | |||
9 | 1-(METHOXYMETHYL)-6-(NAPHTHALEN-2-YL)-3-AZABICYCLO[4.1.0]HEPTANE (ENANTIOMERIC MIX) | Drug Info | [10] | |||
10 | 1H-1,2,3-benzotriazol-1-amine | Drug Info | [12] | |||
11 | 2-(2-(4-tert-Butylphenylthio)ethyl)-1H-imidazole | Drug Info | [13] | |||
12 | 2-(4-Imidazol-1-yl-phenoxymethyl)-pyridine | Drug Info | [11] | |||
13 | 2-Fluoro-4-[5-(3-hydroxyphenyl)-2-thienyl]phenol | Drug Info | [14] | |||
14 | 2-Hexyloxy-5-imidazol-1-yl-pyridine | Drug Info | [11] | |||
15 | 2-[3-(4-Imidazol-1-yl-phenoxy)-propyl]-pyridine | Drug Info | [11] | |||
16 | 3-(6-Methoxynaphthalen-2-yl)pyridin-4-amine | Drug Info | [15] | |||
17 | 3-[3-(4-Imidazol-1-yl-phenoxy)-propyl]-pyridine | Drug Info | [11] | |||
18 | 4-(3-Pent-1-ynyl-benzyl)-1H-imidazole | Drug Info | [16] | |||
19 | 4-(3-Phenylethynyl-benzyl)-1H-imidazole | Drug Info | [16] | |||
20 | 4-(Spiro[chromene-2,4'-piperidine]-4-yl)benzamide | Drug Info | [17] | |||
21 | 4-methylaminomethyl-7-methoxycoumarin | Drug Info | [18] | |||
22 | 4-[2-(4-Imidazol-1-yl-phenoxy)-ethyl]-morpholine | Drug Info | [11] | |||
23 | 4-[3-(4-Imidazol-1-yl-phenoxy)-propyl]-pyridine | Drug Info | [11] | |||
24 | 4-[5-(3-Hydroxyphenyl)-2-thienyl)-2-methyl]phenol | Drug Info | [14] | |||
25 | 4-[5-(3-Hydroxyphenyl)-3-thienyl]-2-methylphenol | Drug Info | [14] | |||
26 | 6-(3,4-DICHLOROPHENYL)-1-[1-(METHYLOXY)-3-BUTEN-1-YL]-3-AZABICYCLO[4.1.0]HEPTANE (DIASTEREOMERIC MIX) | Drug Info | [10] | |||
27 | Bis-(5-pyridin-3-yl-thiophen-2-ylmethyl)-amine | Drug Info | [19] | |||
28 | BMS-694153 | Drug Info | [20] | |||
29 | BS 7581 | Drug Info | [21] | |||
30 | BS 7840 | Drug Info | [21] | |||
31 | BS 9106 | Drug Info | [21] | |||
32 | Desethyl isoquine | Drug Info | [6] | |||
33 | DIHYDROCUBEBIN | Drug Info | [22] | |||
34 | GB-12819 | Drug Info | [21] | |||
35 | GBR 12530 | Drug Info | [21] | |||
36 | GBR-12289 | Drug Info | [21] | |||
37 | GNF-PF-2094 | Drug Info | [23] | |||
38 | GNF-PF-4292 | Drug Info | [24] | |||
39 | GNF-PF-5411 | Drug Info | [24] | |||
40 | Go-Y022 | Drug Info | [9] | |||
41 | ICI-199441 | Drug Info | [25] | |||
42 | Kaempferol-3-O-methyl ether | Drug Info | [26] | |||
43 | Methyl-(5-pyridin-3-yl-thiophen-2-yl)-amine | Drug Info | [19] | |||
44 | ML-3163 | Drug Info | [27] | |||
45 | Prodipine | Drug Info | [24] | |||
46 | SB-210313 | Drug Info | [28] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-regulating Transcription Factors |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
1 | Metabolism of xenobiotics by cytochrome P450 | |||||
2 | Drug metabolism - cytochrome P450 | |||||
3 | Serotonergic synapse | |||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Xenobiotics | |||||
WikiPathways | [+] 7 WikiPathways | + | ||||
1 | Metapathway biotransformation | |||||
2 | Tamoxifen metabolism | |||||
3 | Oxidation by Cytochrome P450 | |||||
4 | Vitamin D Receptor Pathway | |||||
5 | Aripiprazole Metabolic Pathway | |||||
6 | Fatty Acid Omega Oxidation | |||||
7 | Codeine and Morphine Metabolism |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | A study of the effects of large doses of glutethimide that were used for self-poisoning during pregnancy on human fetuses. Toxicol Ind Health. 2008 Feb-Mar;24(1-2):69-78. | |||||
REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7192). | |||||
REF 3 | A comparison of the efficacy of aromatase inhibitors in second-line treatment of metastatic breast cancer. Am J Clin Oncol. 2003 Aug;26(4):S9-16. | |||||
REF 4 | Antimalarial activity of isoquine against Kenyan Plasmodium falciparum clinical isolates and association with polymorphisms in pfcrt and pfmdr1 genes. J Antimicrob Chemother. 2013 Apr;68(4):786-8. | |||||
REF 5 | Neurosteroidogenesis in rat retinas. J Neurochem. 1994 Jul;63(1):86-96. | |||||
REF 6 | Candidate selection and preclinical evaluation of N-tert-butyl isoquine (GSK369796), an affordable and effective 4-aminoquinoline antimalarial for ... J Med Chem. 2009 Mar 12;52(5):1408-15. | |||||
REF 7 | A 3D-QSAR model for CYP2D6 inhibition in the aryloxypropanolamine series. Bioorg Med Chem Lett. 2005 Sep 1;15(17):3816-20. | |||||
REF 8 | Synthetic inhibitors of cytochrome P-450 2A6: inhibitory activity, difference spectra, mechanism of inhibition, and protein cocrystallization. J Med Chem. 2006 Nov 30;49(24):6987-7001. | |||||
REF 9 | Structure-activity relationships for the inhibition of recombinant human cytochromes P450 by curcumin analogues. Eur J Med Chem. 2008 Aug;43(8):1621-31. | |||||
REF 10 | 6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptane: a new potent and selective triple reuptake inhibitor. J Med Chem. 2010 Jul 8;53(13):4989-5001. | |||||
REF 11 | Imidazole derivatives as new potent and selective 20-HETE synthase inhibitors. Bioorg Med Chem Lett. 2004 Jan 19;14(2):333-6. | |||||
REF 12 | Discovery of a N'-hydroxyphenylformamidine derivative HET0016 as a potent and selective 20-HETE synthase inhibitor. Bioorg Med Chem Lett. 2001 Dec 3;11(23):2993-5. | |||||
REF 13 | Role of hydrophobic substituents on the terminal nitrogen of histamine in receptor binding and agonist activity: development of an orally active hi... J Med Chem. 2010 May 13;53(9):3840-4. | |||||
REF 14 | New insights into the SAR and binding modes of bis(hydroxyphenyl)thiophenes and -benzenes: influence of additional substituents on 17beta-hydroxyst... J Med Chem. 2009 Nov 12;52(21):6724-43. | |||||
REF 15 | Overcoming undesirable CYP1A2 inhibition of pyridylnaphthalene-type aldosterone synthase inhibitors: influence of heteroaryl derivatization on pote... J Med Chem. 2008 Aug 28;51(16):5064-74. | |||||
REF 16 | 4-benzyl-1H-imidazoles with oxazoline termini as histamine H3 receptor agonists. J Med Chem. 2008 May 22;51(10):2944-53. | |||||
REF 17 | Spirocyclic delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-3-hydroxy-4-(spiro[chromene-2,4'-piperidine]-4-yl) b... J Med Chem. 2009 Sep 24;52(18):5685-702. | |||||
REF 18 | Exploration of the amine terminus in a novel series of 1,2,4-triazolo-3-yl-azabicyclo[3.1.0]hexanes as selective dopamine D3 receptor antagonists. J Med Chem. 2010 Oct 14;53(19):7129-39. | |||||
REF 19 | 5-substituted, 6-substituted, and unsubstituted 3-heteroaromatic pyridine analogues of nicotine as selective inhibitors of cytochrome P-450 2A6. J Med Chem. 2005 Jan 13;48(1):224-39. | |||||
REF 20 | Discovery of (R)-4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan... J Med Chem. 2008 Aug 28;51(16):4858-61. | |||||
REF 21 | Catalytic site prediction and virtual screening of cytochrome P450 2D6 substrates by consideration of water and rescoring in automated docking. J Med Chem. 2006 Apr 20;49(8):2417-30. | |||||
REF 22 | Potent CYP3A4 inhibitory constituents of Piper cubeba. J Nat Prod. 2005 Jan;68(1):64-8. | |||||
REF 23 | Synthesis and antiplasmodial activity of novel 2,4-diaminopyrimidines. Bioorg Med Chem Lett. 2010 Jan 1;20(1):228-31. | |||||
REF 24 | Development of a pharmacophore for inhibition of human liver cytochrome P-450 2D6: molecular modeling and inhibition studies. J Med Chem. 1993 Apr 30;36(9):1136-45. | |||||
REF 25 | Arylacetamide kappa opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity. Bioorg Med Chem Lett. 2005 May 16;15(10):2647-52. | |||||
REF 26 | Sesquiterpenes and flavonol glycosides from Zingiber aromaticum and their CYP3A4 and CYP2D6 inhibitory activities. J Nat Prod. 2004 Jul;67(7):1079-83. | |||||
REF 27 | Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes. J Med Chem. 2003 Jul 17;46(15):3230-44. | |||||
REF 28 | Pyrimidinylimidazole inhibitors of CSBP/p38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes. Bioorg Med Chem Lett. 1998 Nov 17;8(22):3111-6. |
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