Target Information
Target General Information | Top | |||||
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Target ID |
T37848
(Former ID: TTDS00418)
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Target Name |
Albendazole monooxygenase (CYP3A4)
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Synonyms |
Taurochenodeoxycholate 6-alpha-hydroxylase; Quinine 3-monooxygenase; P450-PCN1; Nifedipine oxidase; NF-25; HLp; Cytochrome P450-PCN1; Cytochrome P450 NF-25; Cytochrome P450 HLp; Cytochrome P450 3A4; Cytochrome P450 3A3; CYPIIIA4; CYPIIIA3; CYP3A3; Albendazole sulfoxidase; Albendazole monooxygenase (sulfoxide-forming); 1,8-cineole 2-exo-monooxygenase
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Gene Name |
CYP3A4
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
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. Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole. Cytochromes P450 are a group of heme-thiolate monooxygenases.
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 |
MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMF
DMECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISI AEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYS MDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICV FPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSI IFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVV NETLRLFPIAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHRDPKYWTEPEKFLPERFS KKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLG GLLQPEKPVVLKVESRDGTVSGA Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
ADReCS ID | BADD_A00232 ; BADD_A00376 ; BADD_A00541 ; BADD_A00659 ; BADD_A01336 ; BADD_A01965 ; BADD_A02053 ; BADD_A02189 ; BADD_A02216 ; BADD_A02978 ; BADD_A03877 ; BADD_A04155 ; BADD_A04220 ; BADD_A04253 ; BADD_A04263 ; BADD_A04424 ; BADD_A05280 ; BADD_A05957 ; BADD_A05962 ; BADD_A06627 | |||||
HIT2.0 ID | T85AXP |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | Curcumin | Drug Info | Phase 3 | Solid tumour/cancer | [2], [3] | |
2 | PMX-53 | Drug Info | Phase 2 | Atopic dermatitis | [4], [5] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 66 Inhibitor drugs | + | ||||
1 | Curcumin | Drug Info | [1] | |||
2 | PMX-53 | Drug Info | [6] | |||
3 | (-)-clusin | Drug Info | [7] | |||
4 | (-)-cubebin | Drug Info | [7] | |||
5 | (-)-cubebinin | Drug Info | [7] | |||
6 | (-)-cubebininolide | Drug Info | [7] | |||
7 | (-)-dihydroclusin | Drug Info | [7] | |||
8 | (-)-thujaplicatintrimethyl ether | Drug Info | [7] | |||
9 | (-)-yatein | Drug Info | [7] | |||
10 | (5-pyridin-3-yl-furan-2-yl)methanethiol | Drug Info | [8] | |||
11 | (8R,8'R)-4-hydroxycubebinone | Drug Info | [7] | |||
12 | (8R,8'R,9'S)-5-methoxyclusin | Drug Info | [7] | |||
13 | 1,1':4',1''-terphenyl-3,3''-diol | Drug Info | [9] | |||
14 | 1,2-Diacetoxylycorine | Drug Info | [10] | |||
15 | 1-(3,4-DICHLOROPHENYL)-6-(METHOXYMETHYL)-3-AZABICYCLO[4.1.0]HEPTANE (ENANTIOMERIC MIX) | Drug Info | [11] | |||
16 | 1-(4-Butoxy-phenyl)-1H-imidazole | Drug Info | [12] | |||
17 | 1-(METHOXYMETHYL)-6-(NAPHTHALEN-2-YL)-3-AZABICYCLO[4.1.0]HEPTANE (ENANTIOMERIC MIX) | Drug Info | [11] | |||
18 | 1-Acetoxy-2-tert-butyldimethylsilyl-oxylycorine | Drug Info | [10] | |||
19 | 1-Acetoxylycorine | Drug Info | [10] | |||
20 | 1H-1,2,3-benzotriazol-1-amine | Drug Info | [13] | |||
21 | 2,5-bis(4-hydroxybenzylidene)cyclopentanone | Drug Info | [1] | |||
22 | 2-(2-(4-tert-Butylphenylthio)ethyl)-1H-imidazole | Drug Info | [14] | |||
23 | 2-(4-Imidazol-1-yl-phenoxymethyl)-pyridine | Drug Info | [12] | |||
24 | 2-Fluoro-4-[5-(3-hydroxyphenyl)-2-thienyl]phenol | Drug Info | [15] | |||
25 | 2-fluoro-5-(3-methylthiophen-2-yl)pyridine | Drug Info | [8] | |||
26 | 2-tert-Butyldimethylsilyloxylycorine | Drug Info | [10] | |||
27 | 2-[3-(4-Imidazol-1-yl-phenoxy)-propyl]-pyridine | Drug Info | [12] | |||
28 | 3,3-(1,3-Thiazole-2,5-diyl)diphenol | Drug Info | [9] | |||
29 | 3-(3-methylthiophen-2-yl)pyridine | Drug Info | [8] | |||
30 | 3-(5-((methylthio)methyl)furan-2-yl)pyridine | Drug Info | [8] | |||
31 | 3-(5-[1,3]dithiolan-2-yl-furan-2-yl)pyridine | Drug Info | [8] | |||
32 | 3-(pyridin-3-yl)prop-2-yn-1-amine | Drug Info | [8] | |||
33 | 3-methoxy-5-(6-methoxynaphthalen-2-yl)pyridine | Drug Info | [16] | |||
34 | 3-[3-(4-Imidazol-1-yl-phenoxy)-propyl]-pyridine | Drug Info | [12] | |||
35 | 3-[3-(4-Methoxybenzyl)naphthalen-2-yl]pyridine | Drug Info | [17] | |||
36 | 3-[5-(4-Hydroxyphenyl)-3-thienyl]phenol | Drug Info | [9] | |||
37 | 4-(6-Methoxynaphthalen-2-yl)isoquinoline | Drug Info | [16] | |||
38 | 4-[2-(4-Imidazol-1-yl-phenoxy)-ethyl]-morpholine | Drug Info | [12] | |||
39 | 4-[3-(4-Imidazol-1-yl-phenoxy)-propyl]-pyridine | Drug Info | [12] | |||
40 | 4-[5-(3-Hydroxyphenyl)-2-thienyl)-2-methyl]phenol | Drug Info | [15] | |||
41 | 4-[5-(3-Hydroxyphenyl)-3-thienyl]-2-methylphenol | Drug Info | [15] | |||
42 | 5-(2-phenethylpiperazin-1-yl)-1H-indazole | Drug Info | [18] | |||
43 | 5-Pyridin-3-yl-thiophene-2-carbaldehyde oxime | Drug Info | [19] | |||
44 | 6-(3,4-DICHLOROPHENYL)-1-[1-(METHYLOXY)-3-BUTEN-1-YL]-3-AZABICYCLO[4.1.0]HEPTANE (DIASTEREOMERIC MIX) | Drug Info | [11] | |||
45 | 6-(3-Hydroxy-phenyl)-naphthalen-2-ol | Drug Info | [20] | |||
46 | 6-Pyridin-3-yl-3,4-dihydronaphthalen-2(1H)-one | Drug Info | [21] | |||
47 | Alpha-Hydroxy-Midazolam | Drug Info | [22] | |||
48 | Alpha-methylcubebin | Drug Info | [7] | |||
49 | BERGAPTOL | Drug Info | [23] | |||
50 | BMS-536924 | Drug Info | [24] | |||
51 | DIETHOXYFLOURESCEIN | Drug Info | [25] | |||
52 | DIHYDROCUBEBIN | Drug Info | [7] | |||
53 | ETHOXYCLUSIN | Drug Info | [7] | |||
54 | Geranylcoumarin | Drug Info | [23] | |||
55 | Go-Y026 | Drug Info | [1] | |||
56 | GSK-8062 | Drug Info | [26] | |||
57 | Heme | Drug Info | [27] | |||
58 | HINOKININ | Drug Info | [7] | |||
59 | JATRORRHIZINE | Drug Info | [28] | |||
60 | MEDIORESINOL | Drug Info | [7] | |||
61 | Methyl-(5-pyridin-3-yl-thiophen-2-yl)-amine | Drug Info | [19] | |||
62 | ML-3163 | Drug Info | [29] | |||
63 | ML-3375 | Drug Info | [29] | |||
64 | ML-3403 | Drug Info | [29] | |||
65 | PALMATINE | Drug Info | [28] | |||
66 | TILIROSIDE | Drug Info | [30] |
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 |
Co-Targets | Top | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-regulating microRNAs |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target-Related Models and Studies | Top | |||||
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Target Validation | ||||||
Target QSAR Model |
References | Top | |||||
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REF 1 | 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 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: 7000). | |||||
REF 3 | Nanocurcumin: a promising therapeutic advancement over native curcumin. Crit Rev Ther Drug Carrier Syst. 2013;30(4):331-68. | |||||
REF 4 | 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: 579). | |||||
REF 5 | PMX-53 as a dual CD88 antagonist and an agonist for Mas-related gene 2 (MrgX2) in human mast cells. Mol Pharmacol. 2011 Jun;79(6):1005-13. | |||||
REF 6 | Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92. | |||||
REF 7 | Potent CYP3A4 inhibitory constituents of Piper cubeba. J Nat Prod. 2005 Jan;68(1):64-8. | |||||
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 | Design, synthesis, biological evaluation and pharmacokinetics of bis(hydroxyphenyl) substituted azoles, thiophenes, benzenes, and aza-benzenes as p... J Med Chem. 2008 Nov 13;51(21):6725-39. | |||||
REF 10 | Selective cytochrome P450 3A4 inhibitory activity of Amaryllidaceae alkaloids. Bioorg Med Chem Lett. 2009 Jun 15;19(12):3233-7. | |||||
REF 11 | 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 12 | Imidazole derivatives as new potent and selective 20-HETE synthase inhibitors. Bioorg Med Chem Lett. 2004 Jan 19;14(2):333-6. | |||||
REF 13 | 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 14 | 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 15 | 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 16 | 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 17 | Novel aldosterone synthase inhibitors with extended carbocyclic skeleton by a combined ligand-based and structure-based drug design approach. J Med Chem. 2008 Oct 9;51(19):6138-49. | |||||
REF 18 | 2-Substituted N-aryl piperazines as novel triple reuptake inhibitors for the treatment of depression, Bioorg. Med. Chem. Lett. 20(13):3941-3945 (2010). | |||||
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 | Design, synthesis, and biological evaluation of (hydroxyphenyl)naphthalene and -quinoline derivatives: potent and selective nonsteroidal inhibitors... J Med Chem. 2008 Apr 10;51(7):2158-69. | |||||
REF 21 | In vivo active aldosterone synthase inhibitors with improved selectivity: lead optimization providing a series of pyridine substituted 3,4-dihydro-... J Med Chem. 2008 Dec 25;51(24):8077-87. | |||||
REF 22 | Design and synthesis of a new fluorescent probe for cytochrome P450 3A4 (CYP 3A4). Bioorg Med Chem Lett. 2003 Nov 3;13(21):3643-5. | |||||
REF 23 | Radical scavenging and cytochrome P450 3A4 inhibitory activity of bergaptol and geranylcoumarin from grapefruit. Bioorg Med Chem. 2007 Jun 1;15(11):3684-91. | |||||
REF 24 | Discovery and evaluation of 4-(2-(4-chloro-1H-pyrazol-1-yl)ethylamino)-3-(6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)py... J Med Chem. 2008 Oct 9;51(19):5897-900. | |||||
REF 25 | 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 26 | Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064. Bioorg Med Chem Lett. 2008 Aug 1;18(15):4339-43. | |||||
REF 27 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
REF 28 | Cytochrome P3A4 inhibitors and other constituents of Fibraurea tinctoria. J Nat Prod. 2007 Dec;70(12):1930-3. | |||||
REF 29 | 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 30 | Isolation of cytochrome P450 inhibitors from strawberry fruit, Fragaria ananassa. J Nat Prod. 2004 Nov;67(11):1839-41. |
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