General Information of the Protein
Protein ID
PT00986
Protein Name
Cytochrome P450 3A4
Secondarily
Protein Name
1,4-cineole 2-exo-monooxygenase
1,8-cineole 2-exo-monooxygenase
Albendazole monooxygenase (sulfoxide-forming)
Albendazole sulfoxidase
CYPIIIA3
CYPIIIA4
Cholesterol 25-hydroxylase
Cytochrome P450 3A3
Cytochrome P450 HLp
Cytochrome P450 NF-25
Cytochrome P450-PCN1
Nifedipine oxidase
Quinine 3-monooxygenase
Gene Name
CYP3A4
Secondarily
Gene Name
CYP3A3
Sequence
MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFDMECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIAEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSMDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVFPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSIIFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVNETLRLFPIAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHRDPKYWTEPEKFLPERFSKKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGGLLQPEKPVVLKVESRDGTVSGA
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Cytochrome P450
>
Cytochrome P450 family 3
>
Cytochrome P450 family 3A
>
Cytochrome P450 3A4
Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:20702771, PubMed:19965576, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:2732228, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:21576599, PubMed:21490593). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:14559847, PubMed:12865317). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:2732228, PubMed:15373842, PubMed:15764715, PubMed:22773874). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:2732228, PubMed:15373842, PubMed:15764715). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981).
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Uniprot ID
Primary ID:
P08684

Secondarily ID:
P05184
Q16757
Q9UK50
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Ensembl ID
ENSG00000160868
HGNC ID
HGNC:2637
Subcellular Location
Endoplasmic reticulum membrane
Microsome membrane
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000023 , BTI-Tn-5B1-4
Compound ID Compound Name Compound Formula
CP0005212
US8987315, Ketoconazole
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C26H28Cl2N4O4
 1
1
IC50 = 16 nM
   TI
   LI
   LO
   TS
CP0030899
1-[(2-chlorophenyl)-diphenylmethyl]imidazole
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C22H17ClN2
 1
1
IC50 = 16 nM
   TI
   LI
   LO
   TS
CP0036175
1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[(2S)-3-methyl-2-{[methyl({[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl})carbamoyl]amino}butanamido]-1,6-diphenylhexan-2-yl]carbamate
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C37H48N6O5S2
 1
1
IC50 = 16 nM
   TI
   LI
   LO
   TS
CP0057530
ECONAZOLE
   Show/Hide
C18H15Cl3N2O
 1
1
IC50 = 50 nM
   TI
   LI
   LO
   TS
CP0072682
Exelderm
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C18H15Cl3N2S
 1
1
IC50 = 70 nM
   TI
   LI
   LO
   TS
CP0094206
CHEBI:7825
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C18H13Cl4N3O
 1
1
IC50 = 90 nM
   TI
   LI
   LO
   TS
CP0063077
1-[2-(2,4-dichlorobenzyl)oxy-2-(2,4-dichlorophenyl)ethyl]imidazole;nitric acid
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C18H14Cl4N2O
 1
1
IC50 = 100 nM
   TI
   LI
   LO
   TS
CP0030226
4-Amino-5-chloro-N-{1-[3-(4-fluoro-phenoxy)-propyl]-3-methoxy-piperidin-4-yl}-2-methoxy-benzamide
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C23H29ClFN3O4
 1
1
IC50 = 300 nM
   TI
   LI
   LO
   TS
CP0040838
(2S)-1-[(2S,4R)-4-benzyl-2-hydroxy-4-{[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]carbamoyl}butyl]-N-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide
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C36H47N5O4
 1
1
IC50 = 400 nM
   TI
   LI
   LO
   TS
CP0076396
ERGOCORNINE
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C31H39N5O5
 1
1
IC50 = 500 nM
   TI
   LI
   LO
   TS
CP0013042
(5R,5aR,8aR,9R)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
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C22H22O8
 1
1
IC50 = 600 nM
   TI
   LI
   LO
   TS
CP0041805
(E)-resveratrol
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C14H12O3
 1
1
IC50 = 600 nM
   TI
   LI
   LO
   TS
CP0047240
(6aR,9R)-N-[(1S,2S,4R,7S)-2-hydroxy-7-(2-methylpropyl)-5,8-dioxo-4-propan-2-yl-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
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C32H41N5O5
 1
1
IC50 = 600 nM
   TI
   LI
   LO
   TS
CP0077040
4-Amino-5-chloro-2-ethoxy-N-[4-(4-fluoro-benzyl)-morpholin-2-ylmethyl]-benzamide; citrate(AS-4370)
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C21H25ClFN3O3
 1
1
IC50 = 700 nM
   TI
   LI
   LO
   TS
CP0085966
2-methyl-1,2-dipyridin-3-ylpropan-1-one
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C14H14N2O
 1
1
IC50 = 800 nM
   TI
   LI
   LO
   TS
CP0041632
ITRAZOLE
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C35H38Cl2N8O4
 1
1
IC50 = 900 nM
   TI
   LI
   LO
   TS
CP0072895
US20230414632, Compound I-a
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C26H33NO6
 1
1
IC50 = 900 nM
   TI
   LI
   LO
   TS
CP0082578
CHEBI:27924
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C6H8N2
 1
1
IC50 = 900 nM
   TI
   LI
   LO
   TS
CP0038005
(3S)-oxolan-3-yl N-[(2S,3R)-4-[(4-aminobenzene)(2-methylpropyl)sulfonamido]-3-hydroxy-1-phenylbutan-2-yl]carbamate
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C25H35N3O6S
 1
1
IC50 = 1000 nM
   TI
   LI
   LO
   TS
CP0045584
(5'alpha)-12'-hydroxy-2'-methyl-5'-(phenylmethyl)ergotoman-3',6',18-trione
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C33H35N5O5
 1
1
IC50 = 1000 nM
   TI
   LI
   LO
   TS
CP0075172
2-(4-fluorophenyl)-4-methoxy-3-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-amine
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C19H15FN4O
 1
1
IC50 = 1000 nM
   TI
   LI
   LO
   TS
CP0666147
Anhydrovinblastine
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C45H54N4O8
 1
1
IC50 = 1000 nM
   TI
   LI
   LO
   TS
CP0666814
FK-506
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C44H69NO12
 1
1
IC50 = 1000 nM
   TI
   LI
   LO
   TS
CP0093295
(S)-10-Dimethylaminomethyl-4-ethyl-4,9-dihydroxy-1,12-dihydro-4H-2-oxa-6,12a-diaza-dibenzo[b,h]fluorene-3,13-dione; hydrochloride
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C23H23N3O5
 1
1
IC50 = 1521.1 nM
   TI
   LI
   LO
   TS
CP0077731
(+)-cis-Diltiazem
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C22H26N2O4S
 1
1
IC50 = 1836.6 nM
   TI
   LI
   LO
   TS
CP0000815
Rapamycin C-7, analog 4
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C51H79NO13
 1
1
IC50 = 2000 nM
   TI
   LI
   LO
   TS
CP0010655
(3S,4aS,8aS)-N-tert-butyl-2-[(2R,3R)-2-hydroxy-3-[(3-hydroxy-2-methylphenyl)formamido]-4-(phenylsulfanyl)butyl]-decahydroisoquinoline-3-carboxamide
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C32H45N3O4S
 1
1
IC50 = 2000 nM
   TI
   LI
   LO
   TS
CP0049270
2-phenylethylhydrazine
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C8H12N2
 1
1
IC50 = 2000 nM
   TI
   LI
   LO
   TS
CP0084033
BROMOCRIPTINE
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C32H40BrN5O5
 1
1
IC50 = 2000 nM
   TI
   LI
   LO
   TS
CP0681030
Docetaxel
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C43H59NO17
 1
1
IC50 = 2000 nM
   TI
   LI
   LO
   TS
CP0076413
DIHYDROERGOCRISTINE MESYLATE
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C36H45N5O8S
 1
1
IC50 = 3000 nM
   TI
   LI
   LO
   TS
CP0669536
(2S)-2-[[(2S)-2-[(2S,3S)-2-[(2R)-2-amino-3-mercaptopropyl]amino]-3-methylpentyl]oxy]-1-oxo-3-phenylpropyl]-amino]-4-(methylsulfonyl)-butanoic acid 1-methylethyl ester
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C26H45N3O6S2
 1
1
IC50 = 3000 nM
   TI
   LI
   LO
   TS
CP0659761
{4-[Bis-(4-dimethylamino-phenyl)-methylene]-cyclohexa-2,5-dienylidene}-dimethyl-ammonium chloride
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C25H30ClN3
 1
1
IC50 = 3633.7 nM
   TI
   LI
   LO
   TS
CP0058675
N-methyl-3-(1-tetracyclo[6.6.2.02,7.09,14]hexadeca-2,4,6,9,11,13-hexaenyl)propan-1-amine
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C20H23N
 1
1
IC50 = 4322 nM
   TI
   LI
   LO
   TS
CP0064411
N-[5-chloro-4-[(4-chlorophenyl)-cyanomethyl]-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide
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C22H14Cl2I2N2O2
 1
1
IC50 = 5000 nM
   TI
   LI
   LO
   TS
CP0072808
7-Methyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid ((2R,5S,10bS)-5-benzyl-10b-hydroxy-2-methyl-3,6-dioxo-octahydro-oxazolo[3,2-a]pyrrolo[2,1-c]pyrazin-2-yl)-amide
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C33H37N5O5
 1
1
IC50 = 5000 nM
   TI
   LI
   LO
   TS
CP0046612
CHEBI:31687
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C19H30O5
 1
1
IC50 = 7000 nM
   TI
   LI
   LO
   TS
CP0114119
2-Ethoxy-3-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-benzoimidazole-4-carboxylic acid(CV-11974)
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C24H20N6O3
 1
1
IC50 = 9000 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0096660
1-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]ethan-1-one
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C26H28Cl2N4O4
 16
1 IC50 = 2.38 nM
2 IC50 = 29.6 nM
3 IC50 = 46 nM
4 IC50 = 55.1 nM
5 IC50 = 65 nM
6 IC50 = 80 nM
7 IC50 = 100 nM
8 IC50 = 136 nM
9 IC50 = 140 nM
10 IC50 = 146 nM
11 IC50 = 200 nM
12 IC50 = 240 nM
13 IC50 = 400 nM
14 IC50 = 21330 nM
15 IC50 < 2000 nM
16 IC50 > 20000 nM
CP0005212
US8987315, Ketoconazole
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C26H28Cl2N4O4
 23
1 IC50 = 4 nM
2 IC50 = 7.8 nM
3 IC50 = 11 nM
4 IC50 = 12 nM
5 IC50 = 13 nM
6 IC50 = 16 nM
7 IC50 = 17 nM
8 IC50 = 22 nM
9 IC50 = 24 nM
10 IC50 = 25 nM
11 IC50 = 40 nM
12 IC50 = 50 nM
13 IC50 = 54 nM
14 IC50 = 60 nM
15 IC50 = 140 nM
16 IC50 = 180 nM
17 IC50 = 182.6 nM
18 IC50 = 199.99 nM
19 IC50 = 240 nM
20 IC50 = 245 nM
21 IC50 = 280 nM
22 IC50 = 500 nM
23 IC50 = 2500 nM
CP0030899
1-[(2-chlorophenyl)-diphenylmethyl]imidazole
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C22H17ClN2
 4
1 IC50 = 20 nM
2 IC50 = 50 nM
3 IC50 = 67 nM
4 IC50 = 300 nM
CP0036175
1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[(2S)-3-methyl-2-{[methyl({[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl})carbamoyl]amino}butanamido]-1,6-diphenylhexan-2-yl]carbamate
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C37H48N6O5S2
 6
1 IC50 = 30 nM
2 IC50 = 50 nM
3 IC50 = 110 nM
4 IC50 = 130 nM
5 Ki < 100 nM
6 Ki = 100 nM
CP0040838
(2S)-1-[(2S,4R)-4-benzyl-2-hydroxy-4-{[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]carbamoyl}butyl]-N-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide
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C36H47N5O4
 2
1 IC50 = 150 nM
2 Ki = 480 nM
CP0063077
1-[2-(2,4-dichlorobenzyl)oxy-2-(2,4-dichlorophenyl)ethyl]imidazole;nitric acid
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C18H14Cl4N2O
 4
1 IC50 = 180 nM
2 IC50 = 850 nM
3 IC50 = 851.14 nM
4 Potency = 501.2 nM
CP0057530
ECONAZOLE
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C18H15Cl3N2O
 2
1 IC50 = 430 nM
2 IC50 = 430.53 nM
CP0010655
(3S,4aS,8aS)-N-tert-butyl-2-[(2R,3R)-2-hydroxy-3-[(3-hydroxy-2-methylphenyl)formamido]-4-(phenylsulfanyl)butyl]-decahydroisoquinoline-3-carboxamide
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C32H45N3O4S
 2
1 IC50 = 550 nM
2 Ki = 480 nM
CP0041632
ITRAZOLE
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C35H38Cl2N8O4
 1
1 IC50 = 700 nM
CP0072808
7-Methyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid ((2R,5S,10bS)-5-benzyl-10b-hydroxy-2-methyl-3,6-dioxo-octahydro-oxazolo[3,2-a]pyrrolo[2,1-c]pyrazin-2-yl)-amide
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C33H37N5O5
 1
1 IC50 = 2999.16 nM
CP0084033
BROMOCRIPTINE
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C32H40BrN5O5
 1
1 IC50 = 2999.16 nM
CP0085966
2-methyl-1,2-dipyridin-3-ylpropan-1-one
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C14H14N2O
 3
1 IC50 = 3000 nM
2 IC50 = 4931.74 nM
3 Potency = 1258.9 nM
CP0038005
(3S)-oxolan-3-yl N-[(2S,3R)-4-[(4-aminobenzene)(2-methylpropyl)sulfonamido]-3-hydroxy-1-phenylbutan-2-yl]carbamate
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C25H35N3O6S
 1
1 Ki = 260 nM
CP0077731
(+)-cis-Diltiazem
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C22H26N2O4S
 4
1 Ki = 500 nM
2 Ki = 2200 nM
3 Km = 23000 nM
4 Potency = 3981.1 nM
CP0041805
(E)-resveratrol
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C14H12O3
 2
1 Ki = 20000 nM
2 Potency = 3981.1 nM
CP0047240
(6aR,9R)-N-[(1S,2S,4R,7S)-2-hydroxy-7-(2-methylpropyl)-5,8-dioxo-4-propan-2-yl-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
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C32H41N5O5
 1
1 Potency = 1000 nM
CP0013042
(5R,5aR,8aR,9R)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
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C22H22O8
 1
1 Potency = 1995.3 nM
CP0077632
ISOPIMPINELLIN
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C13H10O5
 1
1 Potency = 1995.3 nM
CP0020849
2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one
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C15H10O7
 1
1 Potency = 6309.6 nM
CP0046363
4-methoxy-7H-furo[3,2-g][1]benzopyran-7-one
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C12H8O4
 1
1 Potency = 10000 nM
CP0659761
{4-[Bis-(4-dimethylamino-phenyl)-methylene]-cyclohexa-2,5-dienylidene}-dimethyl-ammonium chloride
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C25H30ClN3
 1
1 Potency = 10000 nM
CP0038890
2-PHENYL-4H-BENZO[H]CHROMEN-4-ONE
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C19H12O2
 1
1 Potency = 12589.3 nM
CP0058616
5-Hydroxy-2-methyl-[1,4]naphthoquinone
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C11H8O3
 1
1 Potency = 31622.8 nM
Clinical Information about the Protein
Target 1 ( Albendazole monooxygenase (CYP3A4) )
Target Type Clinical trial Target
Disease 2 Target-related Diseases  2
1 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
2 Atopic dermatitis [ICD-11: EA80]
Clinical Trial Drug(s) 2 Clinical Trial Drugs  2
1 Curcumin Phase 3
Solid tumour/cancer
2 PMX-53 Phase 2
Atopic dermatitis
Target 2 ( CYP3A4 messenger RNA (CYP3A4 mRNA) )
Target Type Clinical trial Target