Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT52TWG3)

• DOT Name: Cytochrome P450 2A6 (CYP2A6)
• Synonyms: EC 1.14.14.-; 1,4-cineole 2-exo-monooxygenase; CYPIIA6; Coumarin 7-hydroxylase; Cytochrome P450 IIA3; Cytochrome P450(I)
• Gene Name: CYP2A6
• Related Disease:
  Coumarin resistance
  Nicotine dependence
• UniProt ID: CP2A6_HUMAN
• PDB ID: 1Z10; 1Z11; 2FDU; 2FDV; 2FDW; 2FDY; 3EBS; 3T3Q; 3T3R; 4EJJ; 4RUI
• EC Number: 1.14.14.-
• Pfam ID: PF00067
• Sequence:
  MLASGMLLVALLVCLTVMVLMSVWQQRKSKGKLPPGPTPLPFIGNYLQLNTEQMYNSLMK
  ISERYGPVFTIHLGPRRVVVLCGHDAVREALVDQAEEFSGRGEQATFDWVFKGYGVVFSN
  GERAKQLRRFSIATLRDFGVGKRGIEERIQEEAGFLIDALRGTGGANIDPTFFLSRTVSN
  VISSIVFGDRFDYKDKEFLSLLRMMLGIFQFTSTSTGQLYEMFSSVMKHLPGPQQQAFQL
  LQGLEDFIAKKVEHNQRTLDPNSPRDFIDSFLIRMQEEEKNPNTEFYLKNLVMTTLNLFI
  GGTETVSTTLRYGFLLLMKHPEVEAKVHEEIDRVIGKNRQPKFEDRAKMPYMEAVIHEIQ
  RFGDVIPMSLARRVKKDTKFRDFFLPKGTEVYPMLGSVLRDPSFFSNPQDFNPQHFLNEK
  GQFKKSDAFVPFSIGKRNCFGEGLARMELFLFFTTVMQNFRLKSSQSPKDIDVSPKHVGF
  ATIPRNYTMSFLPR
• Function: Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
• Tissue Specificity: Liver.
• KEGG Pathway:
  Caffeine metabolism (hsa00232)
  Retinol metabolism (hsa00830)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Drug metabolism - cytochrome P450 (hsa00982)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Chemical carcinogenesis - D. adducts (hsa05204)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  CYP2E1 reactions (R-HSA-211999)
  Xenobiotics (R-HSA-211981)
• BioCyc Pathway: MetaCyc:HS10343-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coumarin resistance	DISR63SG	No Known	Unknown	[1]
Nicotine dependence	DISZD9W7	No Known	Unknown	[2]

This DOT Affected the Biotransformations of 8 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Cytochrome P450 2A6 (CYP2A6) increases the chemical synthesis of Fluorouracil.	[43]
Nicotine	DMWX5CO	Approved	Cytochrome P450 2A6 (CYP2A6) decreases the oxidation of Nicotine.	[44]
Ifosfamide	DMCT3I8	Approved	Cytochrome P450 2A6 (CYP2A6) affects the hydroxylation of Ifosfamide.	[45]
Benzoic acid	DMKB9FI	Approved	Cytochrome P450 2A6 (CYP2A6) increases the chemical synthesis of Benzoic acid.	[28]
Letrozole	DMH07Y3	Approved	Cytochrome P450 2A6 (CYP2A6) increases the oxidation of Letrozole.	[50]
Benzyl alcohol	DMBVYDI	Approved	Cytochrome P450 2A6 (CYP2A6) increases the chemical synthesis of Benzyl alcohol.	[28]
Mononitrophenol	DM4QO9G	Investigative	Cytochrome P450 2A6 (CYP2A6) increases the hydroxylation of Mononitrophenol.	[22]
7-hydroxycoumarin	DMTMNO7	Investigative	Cytochrome P450 2A6 (CYP2A6) increases the chemical synthesis of 7-hydroxycoumarin.	[28]

This DOT Affected the Regulation of Drug Effects of 7 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methimazole	DM25FL8	Approved	Cytochrome P450 2A6 (CYP2A6) increases the metabolism of Methimazole.	[46]
Amodiaquine	DME4RA8	Approved	Cytochrome P450 2A6 (CYP2A6) increases the metabolism of Amodiaquine.	[47]
Cotinine	DMCEZ1B	Approved	Cytochrome P450 2A6 (CYP2A6) decreases the abundance of Cotinine.	[49]
FADROZOLE	DM3C5GZ	Approved	Cytochrome P450 2A6 (CYP2A6) increases the metabolism of FADROZOLE.	[51]
PMID28870136-Compound-52	DMFDERP	Patented	Cytochrome P450 2A6 (CYP2A6) increases the metabolism of PMID28870136-Compound-52.	[54]
SM-10661	DMZYGW0	Discontinued in Phase 2	Cytochrome P450 2A6 (CYP2A6) increases the metabolism of SM-10661.	[51]
Coumarin	DM0N8ZM	Investigative	Cytochrome P450 2A6 (CYP2A6) decreases the metabolism of Coumarin.	[55]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Lamotrigine	DM8SXYG	Approved	Cytochrome P450 2A6 (CYP2A6) increases the activity of Lamotrigine.	[48]
Tegafur	DM31ZQM	Approved	Cytochrome P450 2A6 (CYP2A6) decreases the activity of Tegafur.	[52]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Cytochrome P450 2A6 (CYP2A6) decreases the response to substance of Amiodarone.	[53]
BRN-3548355	DM4KXT0	Investigative	Cytochrome P450 2A6 (CYP2A6) increases the activity of BRN-3548355.	[56]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Cytochrome P450 2A6 (CYP2A6).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cytochrome P450 2A6 (CYP2A6).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cytochrome P450 2A6 (CYP2A6).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytochrome P450 2A6 (CYP2A6).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cytochrome P450 2A6 (CYP2A6).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the activity of Cytochrome P450 2A6 (CYP2A6).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cytochrome P450 2A6 (CYP2A6).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Cytochrome P450 2A6 (CYP2A6).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine increases the expression of Cytochrome P450 2A6 (CYP2A6).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Cytochrome P450 2A6 (CYP2A6).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Cytochrome P450 2A6 (CYP2A6).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Cytochrome P450 2A6 (CYP2A6).	[13]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Cytochrome P450 2A6 (CYP2A6).	[14]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Cytochrome P450 2A6 (CYP2A6).	[15]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[16]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Cytochrome P450 2A6 (CYP2A6).	[17]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Cytochrome P450 2A6 (CYP2A6).	[18]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Cytochrome P450 2A6 (CYP2A6).	[19]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Cytochrome P450 2A6 (CYP2A6).	[20]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[21]
Thioridazine	DM35M8J	Approved	Thioridazine decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[22]
Methoxsalen	DME8FZ9	Approved	Methoxsalen decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[23]
Felodipine	DMOSW35	Approved	Felodipine increases the expression of Cytochrome P450 2A6 (CYP2A6).	[24]
Desipramine	DMT2FDC	Approved	Desipramine decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[22]
Isradipine	DMA5XGH	Approved	Isradipine increases the expression of Cytochrome P450 2A6 (CYP2A6).	[24]
Tranylcypromine	DMGB5RE	Approved	Tranylcypromine decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[23]
Benidipine	DMWNP6B	Phase 4	Benidipine increases the expression of Cytochrome P450 2A6 (CYP2A6).	[24]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[22]
I3C	DMIGFOR	Phase 3	I3C decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[25]
TRYPTAMINE	DMAFPHB	Phase 3	TRYPTAMINE decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[26]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Cytochrome P450 2A6 (CYP2A6).	[27]
PEITC	DMOMN31	Phase 2	PEITC decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cytochrome P450 2A6 (CYP2A6).	[4]
T83193	DMHO29Y	Patented	T83193 decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[29]
Ethylvanillin	DM9WMJ1	Patented	Ethylvanillin decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cytochrome P450 2A6 (CYP2A6).	[30]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Cytochrome P450 2A6 (CYP2A6).	[31]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[29]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Cytochrome P450 2A6 (CYP2A6).	[17]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of Cytochrome P450 2A6 (CYP2A6).	[32]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[33]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of Cytochrome P450 2A6 (CYP2A6).	[33]
Oleic acid	DM54O1Z	Investigative	Oleic acid increases the expression of Cytochrome P450 2A6 (CYP2A6).	[34]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol increases the expression of Cytochrome P450 2A6 (CYP2A6).	[35]
Myricetin	DMTV4L0	Investigative	Myricetin decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[36]
Linoleic acid	DMDGPY9	Investigative	Linoleic acid increases the expression of Cytochrome P450 2A6 (CYP2A6).	[34]
MANGIFERIN	DMWAF5Z	Investigative	MANGIFERIN decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[37]
CITCO	DM0N634	Investigative	CITCO increases the expression of Cytochrome P450 2A6 (CYP2A6).	[38]
Alpha-linolenic acid	DMY64HE	Investigative	Alpha-linolenic acid increases the expression of Cytochrome P450 2A6 (CYP2A6).	[34]
Fibrates	DMFNTMY	Investigative	Fibrates decreases the expression of Cytochrome P450 2A6 (CYP2A6).	[11]
(11-BETA)-11,21-DIHYDROXY-PREGN-4-ENE-3,20-DIONE	DMTPQ84	Investigative	(11-BETA)-11,21-DIHYDROXY-PREGN-4-ENE-3,20-DIONE increases the expression of Cytochrome P450 2A6 (CYP2A6).	[39]
Cinnamic acid	DM340FH	Investigative	Cinnamic acid decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[40]
Purpurin	DMYWRL6	Investigative	Purpurin decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[41]
Fluphenazine	DMIT8LX	Investigative	Fluphenazine decreases the activity of Cytochrome P450 2A6 (CYP2A6).	[22]
1H-Indole-2,3-dione	DMOZ91H	Investigative	1H-Indole-2,3-dione increases the expression of Cytochrome P450 2A6 (CYP2A6).	[42]

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