Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE4EFH8)

• DOT Name: Cytochrome P450 1A1 (CYP1A1)
• Synonyms: CYPIA1; EC 1.14.14.1; Cytochrome P450 form 6; Cytochrome P450-C; Cytochrome P450-P1; Hydroperoxy icosatetraenoate dehydratase; EC 4.2.1.152
• Gene Name: CYP1A1
• UniProt ID: CP1A1_HUMAN
• PDB ID: 4I8V; 6DWM; 6DWN; 6O5Y; 6UDL; 6UDM
• EC Number: 1.14.14.1; 4.2.1.152
• Pfam ID: PF00067
• Sequence:
  MLFPISMSATEFLLASVIFCLVFWVIRASRPQVPKGLKNPPGPWGWPLIGHMLTLGKNPH
  LALSRMSQQYGDVLQIRIGSTPVVVLSGLDTIRQALVRQGDDFKGRPDLYTFTLISNGQS
  MSFSPDSGPVWAARRRLAQNGLKSFSIASDPASSTSCYLEEHVSKEAEVLISTLQELMAG
  PGHFNPYRYVVVSVTNVICAICFGRRYDHNHQELLSLVNLNNNFGEVVGSGNPADFIPIL
  RYLPNPSLNAFKDLNEKFYSFMQKMVKEHYKTFEKGHIRDITDSLIEHCQEKQLDENANV
  QLSDEKIINIVLDLFGAGFDTVTTAISWSLMYLVMNPRVQRKIQEELDTVIGRSRRPRLS
  DRSHLPYMEAFILETFRHSSFVPFTIPHSTTRDTSLKGFYIPKGRCVFVNQWQINHDQKL
  WVNPSEFLPERFLTPDGAIDKVLSEKVIIFGMGKRKCIGETIARWEVFLFLAILLQRVEF
  SVPLGVKVDMTPIYGLTMKHACCEHFQMQLRS
• Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins. 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. 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 C15-alpha and C16-alpha positions. Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation. Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system. Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer. May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid. May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent).
• Tissue Specificity: Lung, lymphocytes and placenta.
• KEGG Pathway:
  Steroid hormone biosynthesis (hsa00140)
  Tryptophan metabolism (hsa00380)
  Retinol metabolism (hsa00830)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Metabolic pathways (hsa01100)
  Ovarian steroidogenesis (hsa04913)
  Chemical carcinogenesis - D. adducts (hsa05204)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Xenobiotics (R-HSA-211981)
  Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET) (R-HSA-2142670)
  Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) (R-HSA-2142816)
  Biosynthesis of protectins (R-HSA-9018681)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 13 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Cytochrome P450 1A1 (CYP1A1) increases the degradation of Estradiol.	[67]
Romidepsin	DMT5GNL	Approved	Cytochrome P450 1A1 (CYP1A1) affects the metabolism of Romidepsin.	[72]
Lapatinib	DM3BH1Y	Approved	Cytochrome P450 1A1 (CYP1A1) increases the metabolism of Lapatinib.	[73]
Dronedarone	DMA8FS5	Approved	Cytochrome P450 1A1 (CYP1A1) increases the metabolism of Dronedarone.	[76]
Acenocoumarol	DMH75KV	Approved	Cytochrome P450 1A1 (CYP1A1) affects the metabolism of Acenocoumarol.	[45]
Steroid derivative 1	DMB0NVQ	Patented	Cytochrome P450 1A1 (CYP1A1) increases the abundance of Steroid derivative 1.	[81]
Nobiletin	DM7R3B6	Preclinical	Cytochrome P450 1A1 (CYP1A1) increases the metabolism of Nobiletin.	[82]
geraniol	DMS3CBD	Investigative	Cytochrome P450 1A1 (CYP1A1) increases the metabolism of geraniol.	[84]
Arachidonic acid	DMUOQZD	Investigative	Cytochrome P450 1A1 (CYP1A1) affects the metabolism of Arachidonic acid.	[85]
Ellipticine	DMHPYSM	Investigative	Cytochrome P450 1A1 (CYP1A1) increases the metabolism of Ellipticine.	[88]
Mepacrine	DMU8L7C	Investigative	Cytochrome P450 1A1 (CYP1A1) increases the metabolism of Mepacrine.	[89]
9-phenanthrol	DMJFBQ1	Investigative	Cytochrome P450 1A1 (CYP1A1) increases the abundance of 9-phenanthrol.	[91]
6-Benzyloxy-9H-purin-2-ylamine	DMFI7A8	Investigative	Cytochrome P450 1A1 (CYP1A1) increases the metabolism of 6-Benzyloxy-9H-purin-2-ylamine.	[93]

This DOT Affected the Biotransformations of 11 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone	DM7HUNW	Approved	Cytochrome P450 1A1 (CYP1A1) increases the hydroxylation of Testosterone.	[68]
Progesterone	DMUY35B	Approved	Cytochrome P450 1A1 (CYP1A1) increases the hydroxylation of Progesterone.	[68]
Estrone	DM5T6US	Approved	Cytochrome P450 1A1 (CYP1A1) increases the hydroxylation of Estrone.	[70]
Melatonin	DMKWFBT	Approved	Cytochrome P450 1A1 (CYP1A1) increases the hydroxylation of Melatonin.	[71]
Mefenamic acid	DMK7HFI	Approved	Cytochrome P450 1A1 (CYP1A1) increases the glutathionylation of Mefenamic acid.	[75]
Imiquimod	DM1TMA3	Approved	Cytochrome P450 1A1 (CYP1A1) increases the chemical synthesis of Imiquimod.	[77]
Almogran	DM7I64Z	Approved	Cytochrome P450 1A1 (CYP1A1) decreases the methylation of Almogran.	[78]
N-DESMETHYLCLOZAPINE	DMVIRN3	Phase 2	Cytochrome P450 1A1 (CYP1A1) increases the chemical synthesis of N-DESMETHYLCLOZAPINE.	[80]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	Cytochrome P450 1A1 (CYP1A1) increases the chemical synthesis of all-trans-4-oxo-retinoic acid.	[86]
2-hydroxy-17beta-estradiol	DMM9Z0B	Investigative	Cytochrome P450 1A1 (CYP1A1) affects the chemical synthesis of 2-hydroxy-17beta-estradiol.	[90]
Chloroben	DMY40UB	Investigative	Cytochrome P450 1A1 (CYP1A1) increases the oxidation of Chloroben.	[94]

This DOT Affected the Drug Response of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Gefitinib	DM15F0X	Approved	Cytochrome P450 1A1 (CYP1A1) increases the response to substance of Gefitinib.	[69]
Propranolol	DM79NTF	Approved	Cytochrome P450 1A1 (CYP1A1) increases the Poisoning and toxicity ADR of Propranolol.	[74]
Phenol	DM1QSM3	Phase 2/3	Cytochrome P450 1A1 (CYP1A1) affects the response to substance of Phenol.	[79]
Glyphosate	DM0AFY7	Investigative	Cytochrome P450 1A1 (CYP1A1) affects the response to substance of Glyphosate.	[83]
Tetramethylbutylphenol	DMW9CH2	Investigative	Cytochrome P450 1A1 (CYP1A1) increases the response to substance of Tetramethylbutylphenol.	[87]
DIOSMETIN	DM4KXIM	Investigative	Cytochrome P450 1A1 (CYP1A1) increases the response to substance of DIOSMETIN.	[92]

98 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Cytochrome P450 1A1 (CYP1A1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cytochrome P450 1A1 (CYP1A1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Cytochrome P450 1A1 (CYP1A1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Cytochrome P450 1A1 (CYP1A1).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Cytochrome P450 1A1 (CYP1A1).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cytochrome P450 1A1 (CYP1A1).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the activity of Cytochrome P450 1A1 (CYP1A1).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine increases the expression of Cytochrome P450 1A1 (CYP1A1).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Cytochrome P450 1A1 (CYP1A1).	[14]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[15]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cytochrome P450 1A1 (CYP1A1).	[16]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Cytochrome P450 1A1 (CYP1A1).	[17]
Menadione	DMSJDTY	Approved	Menadione increases the activity of Cytochrome P450 1A1 (CYP1A1).	[18]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Cytochrome P450 1A1 (CYP1A1).	[19]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Cytochrome P450 1A1 (CYP1A1).	[20]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[21]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the activity of Cytochrome P450 1A1 (CYP1A1).	[22]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Cytochrome P450 1A1 (CYP1A1).	[23]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Cytochrome P450 1A1 (CYP1A1).	[24]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Cytochrome P450 1A1 (CYP1A1).	[25]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[26]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Cytochrome P450 1A1 (CYP1A1).	[27]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Cytochrome P450 1A1 (CYP1A1).	[28]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Cytochrome P450 1A1 (CYP1A1).	[29]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Cytochrome P450 1A1 (CYP1A1).	[30]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Cytochrome P450 1A1 (CYP1A1).	[31]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Clozapine	DMFC71L	Approved	Clozapine decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Cytochrome P450 1A1 (CYP1A1).	[33]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[34]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Cytochrome P450 1A1 (CYP1A1).	[35]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[6]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[36]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Cytochrome P450 1A1 (CYP1A1).	[37]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[6]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Cytochrome P450 1A1 (CYP1A1).	[38]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Cytochrome P450 1A1 (CYP1A1).	[39]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Cytochrome P450 1A1 (CYP1A1).	[40]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[41]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Cytochrome P450 1A1 (CYP1A1).	[42]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[43]
Sorafenib	DMS8IFC	Approved	Sorafenib decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[44]
Imatinib	DM7RJXL	Approved	Imatinib decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Ritonavir	DMU764S	Approved	Ritonavir increases the expression of Cytochrome P450 1A1 (CYP1A1).	[45]
Nefazodone	DM4ZS8M	Approved	Nefazodone decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Dactinomycin	DM2YGNW	Approved	Dactinomycin decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[46]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[47]
Ampicillin	DMHWE7P	Approved	Ampicillin decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[48]
Isoproterenol	DMK7MEY	Approved	Isoproterenol decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[49]
Bezafibrate	DMZDCS0	Approved	Bezafibrate increases the expression of Cytochrome P450 1A1 (CYP1A1).	[50]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Approved	Eicosapentaenoic acid/docosa-hexaenoic acid decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[51]
Dihydroxyacetone	DMM1LG2	Approved	Dihydroxyacetone decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[52]
Penicillamine	DM40EF6	Approved	Penicillamine increases the expression of Cytochrome P450 1A1 (CYP1A1).	[53]
Cantharidin	DMBP5N3	Approved	Cantharidin increases the expression of Cytochrome P450 1A1 (CYP1A1).	[54]
Mebendazole	DMO14SG	Approved	Mebendazole increases the expression of Cytochrome P450 1A1 (CYP1A1).	[42]
Omeprazole	DM471KJ	Approved	Omeprazole increases the expression of Cytochrome P450 1A1 (CYP1A1).	[55]
Cimetidine	DMH61ZB	Approved	Cimetidine decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[56]
Hesperetin	DMKER83	Approved	Hesperetin decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[57]
Clotrimazole	DMMFCIH	Approved	Clotrimazole decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Nifedipine	DMSVOZT	Approved	Nifedipine decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Clofibrate	DMPC1J7	Approved	Clofibrate increases the expression of Cytochrome P450 1A1 (CYP1A1).	[50]
Flutamide	DMK0O7U	Approved	Flutamide increases the activity of Cytochrome P450 1A1 (CYP1A1).	[58]
Busulfan	DMXYJ9C	Approved	Busulfan decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Amodiaquine	DME4RA8	Approved	Amodiaquine increases the activity of Cytochrome P450 1A1 (CYP1A1).	[22]
Nelfinavir mesylate	DMFX6G8	Approved	Nelfinavir mesylate increases the expression of Cytochrome P450 1A1 (CYP1A1).	[42]
Carvedilol	DMHTEAO	Approved	Carvedilol decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Ethacrynic acid	DM60QMR	Approved	Ethacrynic acid increases the expression of Cytochrome P450 1A1 (CYP1A1).	[60]
Sanguinarine	DMDINFS	Approved	Sanguinarine increases the expression of Cytochrome P450 1A1 (CYP1A1).	[61]
Abacavir	DMMN36E	Approved	Abacavir decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Methoxsalen	DME8FZ9	Approved	Methoxsalen decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Clopidogrel	DMOL54H	Approved	Clopidogrel decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Lansoprazole	DMXYLQ3	Approved	Lansoprazole increases the expression of Cytochrome P450 1A1 (CYP1A1).	[55]
Tolcapone	DM8MNVO	Approved	Tolcapone decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Benzbromarone	DMC3YUA	Approved	Benzbromarone decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Terbinafine	DMI6HUW	Approved	Terbinafine decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Zafirlukast	DMHNQOG	Approved	Zafirlukast decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Amlodipine	DMBDAZV	Approved	Amlodipine decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[62]
Plicamycin	DM7C8YV	Approved	Plicamycin decreases the expression of Cytochrome P450 1A1 (CYP1A1).	[64]
Felodipine	DMOSW35	Approved	Felodipine increases the expression of Cytochrome P450 1A1 (CYP1A1).	[65]
Primaquine	DMWQ16I	Approved	Primaquine increases the expression of Cytochrome P450 1A1 (CYP1A1).	[22]
Amiloride	DMRTSGP	Approved	Amiloride decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Riluzole	DMECBWN	Approved	Riluzole decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Acitretin	DM8BKU9	Approved	Acitretin decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Bromocriptine	DMVE3TK	Approved	Bromocriptine decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Pazopanib	DMF57DM	Approved	Pazopanib decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Quinine	DMSWYF5	Approved	Quinine increases the expression of Cytochrome P450 1A1 (CYP1A1).	[22]
Romiplostim	DM3U7SZ	Approved	Romiplostim increases the expression of Cytochrome P450 1A1 (CYP1A1).	[66]
Isradipine	DMA5XGH	Approved	Isradipine increases the expression of Cytochrome P450 1A1 (CYP1A1).	[65]
Danazol	DML8KTN	Approved	Danazol decreases the activity of Cytochrome P450 1A1 (CYP1A1).	[32]
Albendazole	DMYZ57N	Approved	Albendazole increases the expression of Cytochrome P450 1A1 (CYP1A1).	[22]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Prasterone	DM67VKL	Approved	Prasterone decreases the stability of Cytochrome P450 1A1 (CYP1A1).	[59]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cotinine	DMCEZ1B	Approved	Cotinine affects the methylation of Cytochrome P450 1A1 (CYP1A1).	[63]

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