Details of Drug Off-Target (DOT)

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

• DOT Name: Cytochrome P450 3A7 (CYP3A7)
• Synonyms: EC 1.14.14.1; CYPIIIA7; Cytochrome P450-HFLA; P450HLp2
• Gene Name: CYP3A7
• UniProt ID: CP3A7_HUMAN
• PDB ID: 7MK8
• EC Number: 1.14.14.1
• Pfam ID: PF00067
• Sequence:
  MDLIPNLAVETWLLLAVSLILLYLYGTRTHGLFKKLGIPGPTPLPFLGNALSFRKGYWTF
  DMECYKKYRKVWGIYDCQQPMLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKNAISI
  AEDEEWKRIRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKHVFGAYS
  MDVITSTSFGVSIDSLNNPQDPFVENTKKLLRFNPLDPFVLSIKVFPFLTPILEALNITV
  FPRKVISFLTKSVKQIKEGRLKETQKHRVDFLQLMIDSQNSKDSETHKALSDLELMAQSI
  IFIFAGYETTSSVLSFIIYELATHPDVQQKVQKEIDTVLPNKAPPTYDTVLQLEYLDMVV
  NETLRLFPVAMRLERVCKKDVEINGMFIPKGVVVMIPSYVLHHDPKYWTEPEKFLPERFS
  KKNKDNIDPYIYTPFGSGPRNCIGMRFALVNMKLALVRVLQNFSFKPCKETQIPLKLRFG
  GLLLTEKPIVLKAESRDETVSGA
• Function: A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis. 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. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position. Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development. Also involved in the oxidative metabolism of xenobiotics including anticonvulsants.
• Tissue Specificity: Expressed in fetal liver (at protein level).
• KEGG Pathway:
  Steroid hormone biosynthesis (hsa00140)
  Retinol metabolism (hsa00830)
  Metabolic pathways (hsa01100)
  Chemical carcinogenesis - D. adducts (hsa05204)
• Reactome Pathway: Xenobiotics (R-HSA-211981)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 8 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone	DM7HUNW	Approved	Cytochrome P450 3A7 (CYP3A7) increases the hydroxylation of Testosterone.	[25]
Thalidomide	DM70BU5	Approved	Cytochrome P450 3A7 (CYP3A7) increases the hydroxylation of Thalidomide.	[26]
Imatinib	DM7RJXL	Approved	Cytochrome P450 3A7 (CYP3A7) decreases the methylation of Imatinib.	[27]
Estrone	DM5T6US	Approved	Cytochrome P450 3A7 (CYP3A7) increases the hydroxylation of Estrone.	[28]
Tacrolimus	DMZ7XNQ	Approved	Cytochrome P450 3A7 (CYP3A7) decreases the methylation of Tacrolimus.	[29]
Prasterone	DM67VKL	Approved	Cytochrome P450 3A7 (CYP3A7) increases the hydroxylation of Prasterone.	[25]
Dehydroepiandrosterone sulfate	DM4Q80H	Approved	Cytochrome P450 3A7 (CYP3A7) increases the hydroxylation of Dehydroepiandrosterone sulfate.	[28]
HELENALIN	DMMCI4H	Terminated	Cytochrome P450 3A7 (CYP3A7) increases the oxidation of HELENALIN.	[34]

This DOT Affected the Regulation of Drug Effects of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Lapatinib	DM3BH1Y	Approved	Cytochrome P450 3A7 (CYP3A7) increases the metabolism of Lapatinib.	[30]
Amodiaquine	DME4RA8	Approved	Cytochrome P450 3A7 (CYP3A7) increases the metabolism of Amodiaquine.	[31]
Dronedarone	DMA8FS5	Approved	Cytochrome P450 3A7 (CYP3A7) increases the metabolism of Dronedarone.	[32]
Chlorpyrifos	DMKPUI6	Investigative	Cytochrome P450 3A7 (CYP3A7) affects the metabolism of Chlorpyrifos.	[35]
1,4-Naphthoquinone	DMTCMH7	Investigative	Cytochrome P450 3A7 (CYP3A7) increases the abundance of 1,4-Naphthoquinone.	[36]
Fenthion	DMKEG49	Investigative	Cytochrome P450 3A7 (CYP3A7) affects the metabolism of Fenthion.	[37]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorpromazine	DMBGZI3	Phase 3 Trial	Cytochrome P450 3A7 (CYP3A7) decreases the response to substance of Chlorpromazine.	[33]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Cytochrome P450 3A7 (CYP3A7) decreases the response to substance of Amiodarone.	[33]

33 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 3A7 (CYP3A7).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cytochrome P450 3A7 (CYP3A7).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cytochrome P450 3A7 (CYP3A7).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytochrome P450 3A7 (CYP3A7).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cytochrome P450 3A7 (CYP3A7).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cytochrome P450 3A7 (CYP3A7).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cytochrome P450 3A7 (CYP3A7).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine increases the expression of Cytochrome P450 3A7 (CYP3A7).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cytochrome P450 3A7 (CYP3A7).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Cytochrome P450 3A7 (CYP3A7).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Cytochrome P450 3A7 (CYP3A7).	[11]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Cytochrome P450 3A7 (CYP3A7).	[3]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Cytochrome P450 3A7 (CYP3A7).	[12]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Cytochrome P450 3A7 (CYP3A7).	[13]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Cytochrome P450 3A7 (CYP3A7).	[14]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Cytochrome P450 3A7 (CYP3A7).	[15]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Cytochrome P450 3A7 (CYP3A7).	[11]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Cytochrome P450 3A7 (CYP3A7).	[16]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Cytochrome P450 3A7 (CYP3A7).	[3]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Cytochrome P450 3A7 (CYP3A7).	[17]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Cytochrome P450 3A7 (CYP3A7).	[16]
Bosentan	DMIOGBU	Approved	Bosentan affects the expression of Cytochrome P450 3A7 (CYP3A7).	[18]
Omeprazole	DM471KJ	Approved	Omeprazole increases the expression of Cytochrome P450 3A7 (CYP3A7).	[11]
Clotrimazole	DMMFCIH	Approved	Clotrimazole increases the expression of Cytochrome P450 3A7 (CYP3A7).	[16]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cytochrome P450 3A7 (CYP3A7).	[19]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Cytochrome P450 3A7 (CYP3A7).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Cytochrome P450 3A7 (CYP3A7).	[20]
PD-0325901	DM27D4J	Phase 2	PD-0325901 increases the expression of Cytochrome P450 3A7 (CYP3A7).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Cytochrome P450 3A7 (CYP3A7).	[23]
U0126	DM31OGF	Investigative	U0126 increases the expression of Cytochrome P450 3A7 (CYP3A7).	[21]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Cytochrome P450 3A7 (CYP3A7).	[3]
CITCO	DM0N634	Investigative	CITCO increases the activity of Cytochrome P450 3A7 (CYP3A7).	[24]
CI-1040	DMF3DZX	Investigative	CI-1040 increases the expression of Cytochrome P450 3A7 (CYP3A7).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cytochrome P450 3A7 (CYP3A7).	[22]

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