Details of Drug Off-Target (DOT)

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

• DOT Name: Cytochrome P450 1B1 (CYP1B1)
• Synonyms: EC 1.14.14.1; CYPIB1; Hydroperoxy icosatetraenoate dehydratase; EC 4.2.1.152
• Gene Name: CYP1B1
• Related Disease:
  CYP1B1-related glaucoma with or without anterior segment dysgenesis
  Glaucoma 3A
  Anterior segment dysgenesis 6
  Congenital glaucoma
  Peters anomaly
• UniProt ID: CP1B1_HUMAN
• PDB ID: 3PM0; 6IQ5
• EC Number: 1.14.14.1; 4.2.1.152
• Pfam ID: PF00067
• Sequence:
  MGTSLSPNDPWPLNPLSIQQTTLLLLLSVLATVHVGQRLLRQRRRQLRSAPPGPFAWPLI
  GNAAAVGQAAHLSFARLARRYGDVFQIRLGSCPIVVLNGERAIHQALVQQGSAFADRPAF
  ASFRVVSGGRSMAFGHYSEHWKVQRRAAHSMMRNFFTRQPRSRQVLEGHVLSEARELVAL
  LVRGSADGAFLDPRPLTVVAVANVMSAVCFGCRYSHDDPEFRELLSHNEEFGRTVGAGSL
  VDVMPWLQYFPNPVRTVFREFEQLNRNFSNFILDKFLRHCESLRPGAAPRDMMDAFILSA
  EKKAAGDSHGGGARLDLENVPATITDIFGASQDTLSTALQWLLLLFTRYPDVQTRVQAEL
  DQVVGRDRLPCMGDQPNLPYVLAFLYEAMRFSSFVPVTIPHATTANTSVLGYHIPKDTVV
  FVNQWSVNHDPLKWPNPENFDPARFLDKDGLINKDLTSRVMIFSVGKRRCIGEELSKMQL
  FLFISILAHQCDFRANPNEPAKMNFSYGLTIKPKSFKVNVTLRESMELLDSAVQNLQAKE
  TCQ
• 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). Exhibits catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2- and 4-hydroxy E1 and E2. Displays a predominant hydroxylase activity toward E2 at the C-4 position. Metabolizes testosterone and progesterone to B or D ring hydroxylated metabolites. May act as a major enzyme for 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. Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EpETrE) regioisomers, 8,9-, 11,12-, and 14,15- EpETrE, that function as lipid mediators in the vascular system. Additionally, displays dehydratase activity toward oxygenated eicosanoids hydroperoxyeicosatetraenoates (HpETEs). This activity is independent of cytochrome P450 reductase, NADPH, and O2. Also involved in the oxidative metabolism of xenobiotics, particularly converting polycyclic aromatic hydrocarbons and heterocyclic aryl amines procarcinogens to DNA-damaging products. Plays an important role in retinal vascular development. Under hyperoxic O2 conditions, promotes retinal angiogenesis and capillary morphogenesis, likely by metabolizing the oxygenated products generated during the oxidative stress. Also, contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression.
• Tissue Specificity: Expressed in heart, brain, lung, skeletal muscle, kidney, spleen, thymus, prostate, testis, ovary, small intestine, colon, and peripheral blood leukocytes . Expressed in retinal endothelial cells and umbilical vein endothelial cells (at protein level) .
• KEGG Pathway:
  Steroid hormone biosynthesis (hsa00140)
  Tryptophan metabolism (hsa00380)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Ovarian steroidogenesis (hsa04913)
  Chemical carcinogenesis - D. adducts (hsa05204)
  MicroR.s in cancer (hsa05206)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
• Reactome Pathway:
  Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET) (R-HSA-2142670)
  Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) (R-HSA-2142816)
  Defective CYP1B1 causes Glaucoma (R-HSA-5579000)
  Endogenous sterols (R-HSA-211976)
• BioCyc Pathway: MetaCyc:HS06443-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
CYP1B1-related glaucoma with or without anterior segment dysgenesis	DISSND1E	Definitive	Autosomal recessive	[1]
Glaucoma 3A	DISHJWKA	Definitive	Autosomal recessive	[2]
Anterior segment dysgenesis 6	DIS5KQER	Strong	Autosomal dominant	[3]
Congenital glaucoma	DISHN3GO	Supportive	Autosomal dominant	[4]
Peters anomaly	DISERK0M	Supportive	Autosomal dominant	[5]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Daunorubicin	DMQUSBT	Approved	Cytochrome P450 1B1 (CYP1B1) affects the response to substance of Daunorubicin.	[47]
Docetaxel	DMDI269	Approved	Cytochrome P450 1B1 (CYP1B1) affects the response to substance of Docetaxel.	[49]
Amodiaquine	DME4RA8	Approved	Cytochrome P450 1B1 (CYP1B1) decreases the response to substance of Amodiaquine.	[52]

This DOT Affected the Biotransformations of 8 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Estrone	DM5T6US	Approved	Cytochrome P450 1B1 (CYP1B1) increases the hydroxylation of Estrone.	[48]
Melatonin	DMKWFBT	Approved	Cytochrome P450 1B1 (CYP1B1) increases the hydroxylation of Melatonin.	[50]
Vitamin A	DMJ2AH4	Approved	Cytochrome P450 1B1 (CYP1B1) increases the oxidation of Vitamin A.	[51]
N-DESMETHYLCLOZAPINE	DMVIRN3	Phase 2	Cytochrome P450 1B1 (CYP1B1) increases the chemical synthesis of N-DESMETHYLCLOZAPINE.	[54]
Nimesulide	DMR1NMD	Terminated	Cytochrome P450 1B1 (CYP1B1) increases the glutathionylation of Nimesulide.	[55]
Piceatannol	DMYOP45	Investigative	Cytochrome P450 1B1 (CYP1B1) affects the chemical synthesis of Piceatannol.	[56]
Hydroxyestradiol	DMJXQME	Investigative	Cytochrome P450 1B1 (CYP1B1) increases the chemical synthesis of Hydroxyestradiol.	[49]
NSC-26745	DMNX245	Investigative	Cytochrome P450 1B1 (CYP1B1) increases the oxidation of NSC-26745.	[60]

This DOT Affected the Regulation of Drug Effects of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ammonia	DMOEVK6	Approved	Cytochrome P450 1B1 (CYP1B1) affects the metabolism of Ammonia.	[53]
Arachidonic acid	DMUOQZD	Investigative	Cytochrome P450 1B1 (CYP1B1) affects the metabolism of Arachidonic acid.	[51]
1,4-Naphthoquinone	DMTCMH7	Investigative	Cytochrome P450 1B1 (CYP1B1) increases the abundance of 1,4-Naphthoquinone.	[57]
Ellipticine	DMHPYSM	Investigative	Cytochrome P450 1B1 (CYP1B1) increases the metabolism of Ellipticine.	[58]
9-phenanthrol	DMJFBQ1	Investigative	Cytochrome P450 1B1 (CYP1B1) increases the abundance of 9-phenanthrol.	[59]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cytochrome P450 1B1 (CYP1B1).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cytochrome P450 1B1 (CYP1B1).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cytochrome P450 1B1 (CYP1B1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[13]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[15]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[17]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Cytochrome P450 1B1 (CYP1B1).	[18]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[19]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cytochrome P450 1B1 (CYP1B1).	[20]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cytochrome P450 1B1 (CYP1B1).	[22]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[23]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Cytochrome P450 1B1 (CYP1B1).	[18]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Cytochrome P450 1B1 (CYP1B1).	[24]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Cytochrome P450 1B1 (CYP1B1).	[25]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Cytochrome P450 1B1 (CYP1B1).	[26]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Cytochrome P450 1B1 (CYP1B1).	[27]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Cytochrome P450 1B1 (CYP1B1).	[28]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Cytochrome P450 1B1 (CYP1B1).	[29]
Clozapine	DMFC71L	Approved	Clozapine decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Cytochrome P450 1B1 (CYP1B1).	[31]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Cytochrome P450 1B1 (CYP1B1).	[7]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[32]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[7]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Cytochrome P450 1B1 (CYP1B1).	[7]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Cytochrome P450 1B1 (CYP1B1).	[33]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Sorafenib	DMS8IFC	Approved	Sorafenib decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Fluoxetine	DM3PD2C	Approved	Fluoxetine decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Cytochrome P450 1B1 (CYP1B1).	[7]
Imatinib	DM7RJXL	Approved	Imatinib decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Ritonavir	DMU764S	Approved	Ritonavir decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Nefazodone	DM4ZS8M	Approved	Nefazodone decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Dinoprostone	DMTYOPD	Approved	Dinoprostone increases the expression of Cytochrome P450 1B1 (CYP1B1).	[34]
Lovastatin	DM9OZWQ	Approved	Lovastatin decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Omeprazole	DM471KJ	Approved	Omeprazole increases the expression of Cytochrome P450 1B1 (CYP1B1).	[35]
Hesperetin	DMKER83	Approved	Hesperetin decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[36]
Clotrimazole	DMMFCIH	Approved	Clotrimazole decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Nifedipine	DMSVOZT	Approved	Nifedipine decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Lapatinib	DM3BH1Y	Approved	Lapatinib decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Flutamide	DMK0O7U	Approved	Flutamide decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Mefenamic acid	DMK7HFI	Approved	Mefenamic acid decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Carvedilol	DMHTEAO	Approved	Carvedilol decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Clomipramine	DMINRKW	Approved	Clomipramine decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Sanguinarine	DMDINFS	Approved	Sanguinarine increases the expression of Cytochrome P450 1B1 (CYP1B1).	[37]
Abacavir	DMMN36E	Approved	Abacavir decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Methoxsalen	DME8FZ9	Approved	Methoxsalen decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Pentamidine	DMHZJCG	Approved	Pentamidine decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Clopidogrel	DMOL54H	Approved	Clopidogrel decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Lansoprazole	DMXYLQ3	Approved	Lansoprazole increases the expression of Cytochrome P450 1B1 (CYP1B1).	[38]
Pantothenic acid	DM091H2	Approved	Pantothenic acid increases the expression of Cytochrome P450 1B1 (CYP1B1).	[39]
Tolcapone	DM8MNVO	Approved	Tolcapone decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Benzbromarone	DMC3YUA	Approved	Benzbromarone decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Terbinafine	DMI6HUW	Approved	Terbinafine decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Dronedarone	DMA8FS5	Approved	Dronedarone decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Zafirlukast	DMHNQOG	Approved	Zafirlukast decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Amlodipine	DMBDAZV	Approved	Amlodipine decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Plicamycin	DM7C8YV	Approved	Plicamycin decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[40]
Felodipine	DMOSW35	Approved	Felodipine decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Trazodone	DMK1GBJ	Approved	Trazodone decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Primaquine	DMWQ16I	Approved	Primaquine increases the expression of Cytochrome P450 1B1 (CYP1B1).	[38]
Amiloride	DMRTSGP	Approved	Amiloride decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Riluzole	DMECBWN	Approved	Riluzole decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Bromocriptine	DMVE3TK	Approved	Bromocriptine decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Pazopanib	DMF57DM	Approved	Pazopanib decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Isradipine	DMA5XGH	Approved	Isradipine decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Albendazole	DMYZ57N	Approved	Albendazole decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Doxycycline	DM7ICNU	Approved	Doxycycline increases the expression of Cytochrome P450 1B1 (CYP1B1).	[41]
Metoclopramide	DMFA5MY	Approved	Metoclopramide decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Rhucin	DM3ADGP	Approved	Rhucin decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Duloxetine	DM9BI7M	Approved	Duloxetine decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Voriconazole	DMAOL2S	Approved	Voriconazole decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Valdecoxib	DMAY7H4	Approved	Valdecoxib decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
L-tryptophan	DMIBH7M	Approved	L-tryptophan increases the expression of Cytochrome P450 1B1 (CYP1B1).	[42]
Tolvaptan	DMIWFRL	Approved	Tolvaptan decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Phenelzine	DMHIDUE	Approved	Phenelzine decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Tranilast	DME5Y64	Approved	Tranilast affects the expression of Cytochrome P450 1B1 (CYP1B1).	[43]
Chlorzoxazone	DMCYVDT	Approved	Chlorzoxazone decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Succimer	DME81IY	Approved	Succimer decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Cyclofenil	DMT5RMB	Approved	Cyclofenil decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Norethindrone acetate	DMDGCQP	Approved	Norethindrone acetate decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Nilutamide	DMFN07X	Approved	Nilutamide decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Pyrantel	DMG2X3E	Approved	Pyrantel decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Valaciclovir	DMHKS94	Approved	Valaciclovir decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Clevidipine butyrate	DMW4M97	Approved	Clevidipine butyrate decreases the activity of Cytochrome P450 1B1 (CYP1B1).	[30]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cytochrome P450 1B1 (CYP1B1).	[44]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Cytochrome P450 1B1 (CYP1B1).	[45]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[46]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Cytochrome P450 1B1 (CYP1B1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cytochrome P450 1B1 (CYP1B1).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Cytochrome P450 1B1 (CYP1B1).	[21]

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