Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DERD86B)

• DME Name: Cytochrome P450 3A7 (CYP3A7)
• Synonyms: Cytochrome P450 family 3 subfamily A member 7; Cytochrome P450-HFLA; CYP3A7; CYPIIIA7; P450HLp2
• Gene Name: CYP3A7
• UniProt ID: CP3A7_HUMAN
• INTEDE ID: DME0015
• Gene ID: 1551
• EC Number:
  EC: 1.14.14.1
  Oxidoreductase
  Oxygen paired donor oxidoreductase
  Flavin/flavoprotein donor oxidoreductase
  EC: 1.14.14.1
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MDLIPNLAVETWLLLAVSLILLYLYGTRTHGLFKKLGIPGPTPLPFLGNALSFRKGYWTF
  DMECYKKYRKVWGIYDCQQPMLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKNAISI
  AEDEEWKRIRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKHVFGAYS
  MDVITSTSFGVSIDSLNNPQDPFVENTKKLLRFNPLDPFVLSIKVFPFLTPILEALNITV
  FPRKVISFLTKSVKQIKEGRLKETQKHRVDFLQLMIDSQNSKDSETHKALSDLELMAQSI
  IFIFAGYETTSSVLSFIIYELATHPDVQQKVQKEIDTVLPNKAPPTYDTVLQLEYLDMVV
  NETLRLFPVAMRLERVCKKDVEINGMFIPKGVVVMIPSYVLHHDPKYWTEPEKFLPERFS
  KKNKDNIDPYIYTPFGSGPRNCIGMRFALVNMKLALVRVLQNFSFKPCKETQIPLKLRFG
  GLLLTEKPIVLKAESRDETVSGA
• Function: This enzyme is involved in the metabolism of steroid hormones and vitamins during embryogenesis. It catalyzes the hydroxylation of carbon-hydrogen bonds and metabolizes 3beta- hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA) and exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D- ring hydroxylated estrone at the C16-alpha position. It mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development. And it is also involved in the oxidative metabolism of xenobiotics including anticonvulsants.
• KEGG Pathway:
  Chemical carcinogenesis (hsa05204)
  Metabolic pathways (hsa01100)
  Retinol metabolism (hsa00830)
  Steroid hormone biosynthesis (hsa00140)
• Reactome Pathway: Xenobiotics (R-HSA-211981)

Molecular Interaction Atlas (MIA) of This DME

101 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alfentanil	DMVO0UB	Anaesthesia	9A78.6	Approved	[1]
Alprazolam	DMC7XDN	Anxiety		Approved	[1]
Aripiprazole	DM3NUMH	Bipolar I disorder		Approved	[1]
Atazanavir	DMSYRBX	Human immunodeficiency virus infection	1C62	Approved	[2]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[3]
Aztreonam	DMDNJHG	Bacterial infection	1A00-1C4Z	Approved	[4]
Buprenorphine	DMPRI8G	Opioid dependence	6C43.2Z	Approved	[5]
Buspirone	DMBS632	Anxiety disorder	6B00-6B0Z	Approved	[1]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[6]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[1]
Chlorpheniramine	DM5URA2	Allergic rhinitis	CA08.0	Approved	[1]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[7]
Cilostazol	DMZMSCT	Intermittent claudication	BD40.00	Approved	[8]
Cisapride	DMY7PED	Gastroesophageal reflux disease	DA22.Z	Approved	[9]
Clothiapine	DM6K1OA	Schizophrenia	6A20	Approved	[10]
Cobicistat	DM6L4H2	Human immunodeficiency virus infection	1C62	Approved	[11]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[1]
Codeine	DMJX6ZG	Allergic rhinitis	CA08.0	Approved	[12]
Cortisone Acetate	DMG8K57	Acne vulgaris	ED80	Approved	[13]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[12]
Daclatasvir	DMSFK9V	Hepatitis C virus infection	1E51.1	Approved	[14]
Dapsone	DM4LT8A	Acne vulgaris	ED80	Approved	[1]
Delavirdine	DM3NF5G	Human immunodeficiency virus infection	1C62	Approved	[1]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[15]
Dextromethorphan	DMUDJZM	Allergic rhinitis	CA08.0	Approved	[16]
Diazepam	DM08E9O	Alcohol withdrawal		Approved	[1]
Diltiazem	DMAI7ZV	Angina pectoris	BA40	Approved	[17]
Docetaxel	DMDI269	Advanced cancer	2A00-2F9Z	Approved	[1]
Domperidone	DMBDPY0	Gastrointestinal disease	DE2Z	Approved	[1]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[18]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[1]
Estradiol Acetate	DM07U2A	Hormone replacement therapy	8E01	Approved	[1]
Estradiol Cypionate	DM27Z5T	Hormone replacement therapy	8E01	Approved	[1]
Estradiol Valerate	DM8MC6O	Hormone replacement therapy	8E01	Approved	[1]
Estriol	DMOEM2I	Hormone deficiency	5A61.1	Approved	[19]
Ethosuximide	DMDZ9LT	Epilepsy	8A60-8A68	Approved	[20]
Felodipine	DMOSW35	Hypertension	BA00-BA04	Approved	[1]
Fentanyl	DM8WAHT	Analgesia	MB40.8	Approved	[1]
Finasteride	DMWV3TZ	Baldness, male pattern		Approved	[1]
Fluticasone	DMGCSVF	Allergic rhinitis	CA08.0	Approved	[21]
Glibenclamide	DM8JXPZ	Diabetic complication	5A2Y	Approved	[22]
Haloperidol	DM96SE0	Delirium		Approved	[1]
Hydrocortisone	DMGEMB7	Acne vulgaris	ED80	Approved	[23]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[12]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[24]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[1]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[25]
Indinavir	DM0T3YH	Human immunodeficiency virus infection	1C62	Approved	[26]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[1]
Lercanidipine	DMPWSEM	Hypertension	BA00-BA04	Approved	[1]
Levomethadyl acetate hydrochloride	DM429AE	N. A.	N. A.	Approved	[1]
Lidocaine	DML4ZOT	Anaesthesia	9A78.6	Approved	[1]
Lorlatinib	DMICDLV	Non-small-cell lung cancer	2C25.Y	Approved	[27]
Methadone	DMTW6IU	Advanced cancer	2A00-2F9Z	Approved	[28]
Metronidazole	DMTIVEN	Abscess		Approved	[29]
Midazolam	DMXOELT	Agitation	6A70.3	Approved	[12]
Nateglinide	DMLK2QH	Diabetic complication	5A2Y	Approved	[1]
Nelfinavir mesylate	DMFX6G8	N. A.	N. A.	Approved	[26]
Nevirapine	DM6HX9B	Human immunodeficiency virus infection	1C62	Approved	[18]
Nisoldipine	DM7ISKJ	Hypertension	BA00-BA04	Approved	[1]
Nitrendipine	DM21C09	Hypertension	BA00-BA04	Approved	[1]
Norethindrone acetate	DMDGCQP	N. A.	N. A.	Approved	[30]
Ondansetron	DMOTQ1I	Chemotherapy-induced nausea	MD90	Approved	[31]
Ornidazole	DM6QHDJ	Amoebiasis	1A36	Approved	[32]
Oxazepam	DMXNZM4	Alcohol withdrawal delirium		Approved	[33]
Phenobarbital	DMXZOCG	Cluster headache	8A81.0	Approved	[34]
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[35]
Pimozide	DMW83TP	Schizophrenia	6A20	Approved	[1]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[12]
Praziquantel	DMOU1PK	Flatworm infection	1F70-1F86	Approved	[36]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[37]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[38]
Quetiapine	DM1N62C	Anorexia nervosa cachexia	6B80	Approved	[39]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[1]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[1]
Ritonavir	DMU764S	Human immunodeficiency virus infection	1C62	Approved	[40]
Salmeterol	DMIEU69	Allergic asthma	CA23.0	Approved	[1]
Saquinavir	DMG814N	Human immunodeficiency virus infection	1C62	Approved	[26]
Sildenafil citrate	DMSWJ5X	N. A.	N. A.	Approved	[1]
Sirolimus	DMGW1ID	Advanced cancer	2A00-2F9Z	Approved	[1]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[1]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[1]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[1]
Temsirolimus	DMS104F	Renal cell carcinoma	2C90	Approved	[1]
Testosterone cypionate	DMC1TEV	N. A.	N. A.	Approved	[23]
Testosterone enanthate	DMB6871	N. A.	N. A.	Approved	[23]
Testosterone undecanoate	DMZO10Y	Hypogonadism	5A61.0	Approved	[23]
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[1]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[41]
Triamcinolone diacetate	DM7LRKD	N. A.	N. A.	Approved	[42]
Triazolam	DMETYK5	Insomnia	7A00-7A0Z	Approved	[1]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[43]
Vincristine	DMINOX3	Acute lymphoblastic leukaemia	2A85	Approved	[1]
Vindesine	DMVR628	Acute lymphoblastic leukaemia	2A85	Approved	[44]
Zalcitabine	DMH7MUV	Human immunodeficiency virus infection	1C62	Approved	[45]
Zaleplon	DMGFWSM	Insomnia	7A00-7A0Z	Approved	[1]
Zolpidem	DMWOSKJ	Insomnia	7A00-7A0Z	Approved	[46]
Zonisamide	DM0DTF7	Alcohol dependence	6C40.2	Approved	[47]
Aminophenazone	DMY2AH1	N. A.	N. A.	Phase 4	[12]
Chlorphenamine	DM6C4YJ	Allergic rhinitis	CA08.0	Phase 4	[1]
Prasterone sulfate	DMWRYUH	N. A.	N. A.	Phase 4	[48]

2 Clinical Trial Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GLYCYRRHIZIN	DM8M2N3	Influenza virus infection	1E30-1E32	Phase 3	[49]
Linopirdine	DM0ZOGX	Cognitive impairment	6D71	Phase 3	[50]

2 Discontinued Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Astemizole	DM2HN6Q	Allergic rhinitis	CA08.0	Withdrawn from market	[1]
Terfenadine	DM4KLPT	Allergy	4A80-4A85	Withdrawn from market	[1]

1 Preclinical Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Oxycodone hydrochloride	DMCA7LN	Chronic pain	MG30	Application submitted	[51]

2 Investigative Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Erythromycin salnacedin	DM0PHEW	Discovery agent	N.A.	Investigative	[18]
Ethylmorphine	DM0YROF	Discovery agent	N.A.	Investigative	[12]

References

• [1] Drug Interactions Flockhart Table
• [2] Atazanavir: effects on P-glycoprotein transport and CYP3A metabolism in vitro. Drug Metab Dispos. 2005 Jun;33(6):764-70.
• [3] Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers.
• [4] Aztreonam decreases hepatic microsomal cytochrome P450 in cynomolgus monkeys. Pharmacology. 1994 Mar;48(3):137-42.
• [5] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [6] CYP3A4 and CYP3A7-mediated carbamazepine 10,11-epoxidation are activated by differential endogenous steroids. Drug Metab Dispos. 2003 Apr;31(4):432-8.
• [7] CYP3A7, CYP3A5, CYP3A4, and ABCB1 genetic polymorphisms, cyclosporine concentration, and dose requirement in transplant recipients. Ther Drug Monit. 2008 Dec;30(6):689-99.
• [8] Effects of CYP3A inhibition on the metabolism of cilostazol. Clin Pharmacokinet. 1999;37 Suppl 2:61-8.
• [9] Interaction of cisapride with the human cytochrome P450 system: metabolism and inhibition studies. Drug Metab Dispos. 2000 Jul;28(7):789-800.
• [10] Biotransformation of post-clozapine antipsychotics: pharmacological implications. Clin Pharmacokinet. 2000 May;38(5):393-414.
• [11] Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity. Clin Pharmacol Ther. 2010 Mar;87(3):322-9.
• [12] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [13] Comparative pharmacokinetics and metabolism studies in lean and diet- induced obese mice: an animal efficacy model for 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors. Drug Metab Lett. 2011 Jan;5(1):55-63.
• [14] Daclatasvir: a NS5A replication complex inhibitor for hepatitis C infection. Ann Pharmacother. 2016 Jan;50(1):39-46.
• [15] Cytotoxicity of chloroacetanilide herbicide alachlor in HepG2 cells independent of CYP3A4 and CYP3A7. Food Chem Toxicol. 2007 May;45(5):871-7.
• [16] Characterization of dextromethorphan N-demethylation by human liver microsomes. Contribution of the cytochrome P450 3A (CYP3A) subfamily. Biochem Pharmacol. 1994 Jul 5;48(1):173-82.
• [17] FDA Drug Development and Drug Interactions
• [18] Helices F-G are important for the substrate specificities of CYP3A7. Drug Metab Dispos. 2007 Mar;35(3):484-92.
• [19] Expression and cyclic variability of CYP3A4 and CYP3A7 isoforms in human endometrium and cervix during the menstrual cycle. Drug Metab Dispos. 2003 Jan;31(1):1-6.
• [20] Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of ethosuximide by human hepatic microsomal enzymes. Xenobiotica. 2003 Mar;33(3):265-76.
• [21] Biotransformation of fluticasone: in vitro characterization. Drug Metab Dispos. 2006 Jun;34(6):1035-40.
• [22] Identification of CYP3A7 for glyburide metabolism in human fetal livers. Biochem Pharmacol. 2014 Dec 15;92(4):690-700.
• [23] Steroid hydroxylation by human fetal CYP3A7 and human NADPH-cytochrome P450 reductase coexpressed in insect cells using baculovirus. Res Commun Mol Pathol Pharmacol. 1998 Apr;100(1):15-28.
• [24] Application of liquid chromatography/mass spectrometry in accelerating the identification of human liver cytochrome P450 isoforms involved in the metabolism of iloperidone. J Pharmacol Exp Ther. 1998 Sep;286(3):1285-93.
• [25] Catalysis of drug oxidation during embryogenesis in human hepatic tissues using imipramine as a model substrate. Drug Metab Dispos. 1999 Nov;27(11):1306-8.
• [26] Differential inhibition of cytochrome P450 3A4, 3A5 and 3A7 by five human immunodeficiency virus (HIV) protease inhibitors in vitro. Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):79-85.
• [27] Product characteristics of Lorviqua.
• [28] Methadone metabolism and drug-drug interactions: in vitro and in vivo literature review. J Pharm Sci. 2018 Dec;107(12):2983-2991.
• [29] The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.
• [30] The interaction between St John's wort and an oral contraceptive. Clin Pharmacol Ther. 2003 Dec;74(6):525-35.
• [31] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. Drug Metab Dispos. 1995 Nov;23(11):1225-30.
• [32] Effect of ketoconazole on the pharmacokinetics of ornidazole--a possible role of p-glycoprotein and CYP3A. Drug Metabol Drug Interact. 2006;22(1):67-77.
• [33] Cytochrome P450 enzyme activity and protein expression in primary porcine enterocyte and hepatocyte cultures. Xenobiotica. 2000 Jan;30(1):27-46.
• [34] Regulation of human liver cytochromes P-450 in family 3A in primary and continuous culture of human hepatocytes. Hepatology. 1993 Nov;18(5):1254-62.
• [35] PharmGKB summary: phenytoin pathway. Pharmacogenet Genomics. 2012 Jun;22(6):466-70.
• [36] Rifampin markedly decreases plasma concentrations of praziquantel in healthy volunteers. Clin Pharmacol Ther. 2002 Nov;72(5):505-13.
• [37] The role of cytochrome P450 3A (CYP3A) isoform(s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver. J Steroid Biochem Mol Biol. 1993 Jan;44(1):61-7.
• [38] The influence of diltiazem versus cimetidine on propranolol metabolism. J Clin Pharmacol. 1992 Dec;32(12):1099-104.
• [39] A liquid chromatographic-electrospray-tandem mass spectrometric method for quantitation of quetiapine in human plasma and liver microsomes: application to study in vitro metabolism. J Anal Toxicol. 2004 Sep;28(6):443-8.
• [40] Effect of extended exposure to grapefruit juice on cytochrome P450 3A activity in humans: comparison with ritonavir. Clin Pharmacol Ther. 2006 Mar;79(3):243-54.
• [41] Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8.
• [42] Metabolic pathways of inhaled glucocorticoids by the CYP3A enzymes. Drug Metab Dispos. 2013 Feb;41(2):379-89.
• [43] Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos. 2004 Feb;32(2):259-66.
• [44] Structural perspectives of the CYP3A family and their small molecule modulators in drug metabolism. 2019, 3(3), 132-142.
• [45] Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations. Clin Pharmacokinet. 1997 Mar;32(3):194-209.
• [46] Principles of Clinical Pharmacology (Third Edition). 2012, Pages 417-436
• [47] Differential catalytic properties in metabolism of endogenous and exogenous substrates among CYP3A enzymes expressed in COS-7 cells. Biochim Biophys Acta. 1998 May 8;1380(3):297-304.
• [48] CYP3A7*1C polymorphism, serum dehydroepiandrosterone sulfate level, and bone mineral density in postmenopausal women. Calcif Tissue Int. 2007 Mar;80(3):154-9.
• [49] Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010 Aug;66(8):805-810.
• [50] Induction of cytochromes P-450 2B and 3A in mice following the dietary administration of the novel cognitive enhancer linopirdine. Drug Metab Dispos. 1994 Jan-Feb;22(1):65-73.
• [51] Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes. Drug Metab Dispos. 2004 Apr;32(4):447-54.