Details of Drug-Metabolizing Enzyme (DME)

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

DME Name Cytochrome P450 2C18 (CYP2C18)
Synonyms Cytochrome P450 family 2 subfamily C member 18; Cytochrome P450-6b/29c; CYP2C18; CYPIIC18
Gene Name CYP2C18
UniProt ID
CP2CI_HUMAN
INTEDE ID
DME0017
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
1562
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
MDPAVALVLCLSCLFLLSLWRQSSGRGRLPSGPTPLPIIGNILQLDVKDMSKSLTNFSKV
YGPVFTVYFGLKPIVVLHGYEAVKEALIDHGEEFSGRGSFPVAEKVNKGLGILFSNGKRW
KEIRRFCLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTNASPCDPTFILGCAPCNVICS
VIFHDRFDYKDQRFLNLMEKFNENLRILSSPWIQVCNNFPALIDYLPGSHNKIAENFAYI
KSYVLERIKEHQESLDMNSARDFIDCFLIKMEQEKHNQQSEFTVESLIATVTDMFGAGTE
TTSTTLRYGLLLLLKYPEVTAKVQEEIECVVGRNRSPCMQDRSHMPYTDAVVHEIQRYID
LLPTNLPHAVTCDVKFKNYLIPKGTTIITSLTSVLHNDKEFPNPEMFDPGHFLDKSGNFK
KSDYFMPFSAGKRMCMGEGLARMELFLFLTTILQNFNLKSQVDPKDIDITPIANAFGRVP
PLYQLCFIPV
Function This enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
KEGG Pathway
Chemical carcinogenesis (hsa05204 )
Metabolic pathways (hsa01100 )
Retinol metabolism (hsa00830 )
Serotonergic synapse (hsa04726 )
Reactome Pathway
Xenobiotics (R-HSA-211981 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
26 Approved Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Buprenorphine DMPRI8G Pain MG30-MG3Z Approved [1]
Clobazam - Lundbeck DMW1OQ0 Anxiety disorder 6B00-6B0Z Approved [2]
Clotiazepam DM59AZT Anxiety disorder 6B00-6B0Z Approved [3]
Cyclophosphamide DM4O2Z7 Solid tumour/cancer 2A00-2F9Z Approved [4]
Dapsone DM4LT8A Pneumocystis pneumonia CA40.20 Approved [5]
Diazepam DM08E9O Epilepsy 8A60-8A68 Approved [6]
Diclofenac DMPIHLS Osteoarthritis FA00-FA05 Approved [7]
Ifosfamide DMCT3I8 Solid tumour/cancer 2A00-2F9Z Approved [4]
Imipramine DM2NUH3 Depression 6A70-6A7Z Approved [8]
Istradefylline DM20VSK Parkinson disease 8A00.0 Approved [9]
Lansoprazole DMXYLQ3 Duodenal ulcer DA63 Approved [10]
Lidocaine DML4ZOT Anaesthesia 9A78.6 Approved [11]
Mephenytoin DM5UGDK Epilepsy 8A60-8A68 Approved [12]
Methadone DMTW6IU Dry cough MD12 Approved [13]
Omeprazole DM471KJ Gastroesophageal reflux disease DA22.Z Approved [14]
Perphenazine DMA4MRX Schizophrenia 6A20 Approved [15]
Phenobarbital DMXZOCG Seizure disorder 8A6Z Approved [16]
Phenytoin DMNOKBV Epilepsy 8A60-8A68 Approved [11]
Propofol DMB4OLE Anaesthesia 9A78.6 Approved [17]
Thalidomide DM70BU5 Multiple myeloma 2A83 Approved [18]
Tolbutamide DM02AWV Non-insulin dependent diabetes 5A11 Approved [11]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [19]
Verapamil DMA7PEW Hypertension BA00-BA04 Approved [11]
Warfarin DMJYCVW Atrial fibrillation BC81.3 Approved [20]
Aminophenazone DMY2AH1 Anaesthesia 9A78.6 Phase 4 [21]
Etizolam DM8TNX3 Insomnia 7A00-7A0Z Phase 4 [22]
⏷ Show the Full List of 26 Approved Drug(s)
1 Clinical Trial Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Salvinorin A DMJ3HQY Cerebral vasospasm BA85.Z Phase 1 [23]
1 Investigative Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Phenazone DMCE985 Discovery agent N.A. Investigative [24]

Molecular Expression Atlas (MEA) of This DME

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DME
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Acute myelocytic leukaemia 2B33.1 Bone marrow 5.97E-02 3.02E-02 2.52E-01
Alopecia ED70 Skin from scalp 2.55E-01 1.37E-01 2.32E-01
Alzheimer's disease 8A20 Entorhinal cortex 5.67E-02 2.96E-03 1.50E-02
Ankylosing spondylitis FA92.0 Pheripheral blood 1.60E-01 -8.74E-02 -7.78E-01
Aortic stenosis BB70 Calcified aortic valve 8.69E-01 1.04E-01 2.17E-01
Apnea 7A40 Hyperplastic tonsil 4.52E-01 -1.66E-01 -1.63E-01
Arthropathy FA00-FA5Z Peripheral blood 9.78E-01 -2.44E-02 -4.19E-01
Asthma CA23 Nasal and bronchial airway 7.25E-03 2.30E-01 3.62E-01
Atopic dermatitis EA80 Skin 6.98E-08 -1.33E+00 -3.64E+00
Autism 6A02 Whole blood 9.73E-01 1.54E-02 1.17E-01
Autoimmune uveitis 9A96 Peripheral monocyte 3.73E-02 -1.49E-01 -1.01E+00
Autosomal dominant monocytopenia 4B04 Whole blood 6.59E-01 -4.73E-02 -5.62E-01
Bacterial infection of gingival 1C1H Gingival tissue 2.88E-21 -9.98E-01 -1.87E+00
Batten disease 5C56.1 Whole blood 8.67E-03 1.09E-01 1.43E+00
Behcet's disease 4A62 Peripheral blood 4.82E-01 6.43E-03 3.61E-02
Bipolar disorder 6A60-6A6Z Prefrontal cortex 4.76E-01 3.41E-03 2.77E-02
Bladder cancer 2C94 Bladder tissue 4.90E-08 6.12E-01 3.23E+00
Breast cancer 2C60-2C6Z Breast tissue 2.61E-18 -2.07E-01 -7.86E-01
Cardioembolic stroke 8B11.20 Whole blood 7.52E-01 5.93E-02 3.34E-01
Cervical cancer 2C77 Cervical tissue 1.32E-04 -1.25E+00 -1.38E+00
Childhood onset rheumatic disease FA20.Z Peripheral blood 5.97E-01 2.97E-02 2.05E-01
Chronic hepatitis C 1E51.1 Whole blood 4.22E-01 4.43E-02 3.32E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 8.28E-05 1.33E-01 1.20E+00
Chronic obstructive pulmonary disease CA22 Small airway epithelium 1.51E-03 -1.83E-01 -2.01E-01
Chronic rhinosinusitis CA0A Sinus mucosa tissue 4.39E-01 6.55E-02 1.91E-01
Colon cancer 2B90 Colon tissue 1.78E-29 -1.31E+00 -1.29E+00
Coronary artery disease BA80-BA8Z Peripheral blood 6.77E-01 6.64E-03 6.02E-02
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 7.76E-01 6.42E-02 2.57E-01
Endometriosis GA10 Endometrium tissue 4.02E-02 1.05E-01 4.90E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 2.38E-01 -8.56E-02 -9.02E-01
Familial hypercholesterolemia 5C80.00 Whole blood 1.22E-01 -8.05E-02 -5.31E-01
Gastric cancer 2B72 Gastric tissue 7.24E-01 -1.77E+00 -5.71E-01
Glioblastopma 2A00.00 Nervous tissue 6.76E-05 -6.83E-02 -3.08E-01
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 9.88E-02 -9.54E-03 -7.00E-01
Glioma 2A00.0Y-2A00.0Z White matter tissue 1.04E-02 -1.72E-01 -8.08E-01
Head and neck cancer 2D42 Head and neck tissue 1.81E-21 -1.60E+00 -1.46E+00
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 3.64E-01 -2.28E-03 -9.87E-03
Huntington's disease 8A01.10 Whole blood 7.62E-01 2.68E-03 4.91E-02
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 6.01E-02 4.39E-01 1.83E+00
Immunodeficiency 4A00-4A20 Peripheral blood 2.58E-02 1.12E-01 1.35E+00
Influenza 1E30 Whole blood 1.79E-02 2.49E-01 2.12E+00
Interstitial cystitis GC00.3 Bladder tissue 3.31E-01 6.10E-02 1.52E+00
Intracranial aneurysm 8B01.0 Intracranial artery 2.65E-01 1.58E-02 9.62E-02
Irritable bowel syndrome DD91.0 Rectal colon tissue 1.12E-04 3.85E-01 6.88E-01
Ischemic stroke 8B11 Peripheral blood 6.98E-02 2.13E-02 1.55E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 1.35E-01 3.54E-02 2.15E-01
Lateral sclerosis 8B60.4 Skin 1.79E-01 9.66E-02 1.48E+00
Lateral sclerosis 8B60.4 Cervical spinal cord 2.12E-01 6.84E-02 4.60E-01
Liver cancer 2C12.0 Liver tissue 2.25E-42 -1.97E+00 -3.37E+00
Liver failure DB99.7-DB99.8 Liver tissue 5.76E-03 -2.41E+00 -3.50E+01
Lung cancer 2C25 Lung tissue 9.85E-27 -8.91E-03 -2.97E-02
Lupus erythematosus 4A40 Whole blood 3.64E-02 3.87E-03 1.26E-02
Major depressive disorder 6A70-6A7Z Hippocampus 7.90E-01 3.72E-02 2.95E-01
Major depressive disorder 6A70-6A7Z Whole blood 1.08E-01 4.49E-02 2.47E-01
Melanoma 2C30 Skin 3.32E-02 -1.60E+00 -1.47E+00
Multiple myeloma 2A83.1 Peripheral blood 2.11E-01 1.05E-01 8.95E-01
Multiple myeloma 2A83.1 Bone marrow 3.89E-01 -1.24E-01 -5.56E-01
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 6.12E-01 -6.44E-02 -3.17E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 1.33E-01 1.50E-02 7.93E-02
Myelofibrosis 2A20.2 Whole blood 1.62E-03 1.65E-01 1.43E+00
Myocardial infarction BA41-BA50 Peripheral blood 7.90E-03 2.71E-01 5.74E-01
Myopathy 8C70.6 Muscle tissue 1.57E-02 -2.20E-01 -1.93E+00
Neonatal sepsis KA60 Whole blood 7.32E-02 2.95E-02 2.44E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 2.57E-03 -4.57E-01 -1.48E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 5.62E-01 -9.46E-02 -1.99E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 9.65E-02 1.59E-02 2.40E-01
Olive pollen allergy CA08.00 Peripheral blood 1.83E-01 1.22E-01 6.90E-01
Oral cancer 2B6E Oral tissue 2.57E-05 -1.72E+00 -1.19E+00
Osteoarthritis FA00-FA0Z Synovial tissue 9.26E-01 1.06E-01 4.11E-01
Osteoporosis FB83.1 Bone marrow 1.65E-01 1.06E-01 6.94E-01
Ovarian cancer 2C73 Ovarian tissue 2.01E-05 4.55E-02 2.54E-01
Pancreatic cancer 2C10 Pancreas 2.05E-02 1.48E+00 9.61E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 3.07E-01 2.41E-02 1.75E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 3.39E-01 7.70E-03 6.72E-02
Pituitary cancer 2D12 Pituitary tissue 1.81E-04 4.78E-01 2.70E+00
Pituitary gonadotrope tumour 2D12 Pituitary tissue 1.12E-03 1.05E+00 9.93E+00
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 4.85E-01 1.31E-02 8.72E-02
Polycythemia vera 2A20.4 Whole blood 5.35E-06 8.55E-02 8.68E-01
Pompe disease 5C51.3 Biceps muscle 1.39E-01 -6.88E-02 -4.99E-01
Preterm birth KA21.4Z Myometrium 1.01E-01 -5.88E-02 -1.17E+00
Prostate cancer 2C82 Prostate 1.18E-03 -6.44E-01 -1.57E+00
Psoriasis EA90 Skin 8.93E-21 9.68E-01 1.50E+00
Rectal cancer 2B92 Rectal colon tissue 8.81E-02 -4.69E-01 -6.59E-01
Renal cancer 2C90-2C91 Kidney 7.40E-01 -1.19E-01 -7.13E-01
Retinoblastoma 2D02.2 Uvea 6.16E-03 -8.14E-02 -1.13E+00
Rheumatoid arthritis FA20 Synovial tissue 7.46E-02 -1.26E-01 -3.29E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 8.33E-01 -5.95E-02 -1.34E-01
Schizophrenia 6A20 Prefrontal cortex 7.67E-01 9.79E-03 5.37E-02
Schizophrenia 6A20 Superior temporal cortex 4.69E-01 -3.64E-02 -3.49E-01
Scleroderma 4A42.Z Whole blood 9.84E-01 1.04E-01 4.68E-01
Seizure 8A60-8A6Z Whole blood 7.17E-01 4.21E-02 4.07E-01
Sensitive skin EK0Z Skin 4.66E-02 4.56E-01 7.85E-01
Sepsis with septic shock 1G41 Whole blood 3.75E-11 5.25E-02 3.84E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 2.52E-01 3.56E-01 8.08E-01
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 3.20E-01 4.97E-03 3.91E-02
Simpson golabi behmel syndrome LD2C Adipose tissue 9.67E-01 1.75E-02 1.37E-01
Sjogren's syndrome 4A43.2 Salivary gland tissue 6.28E-01 -6.73E-03 -2.49E-02
Skin cancer 2C30-2C3Z Skin 2.84E-47 -1.54E+00 -2.62E+00
Thrombocythemia 3B63 Whole blood 3.72E-01 -1.01E-02 -8.65E-02
Thrombocytopenia 3B64 Whole blood 6.89E-01 1.03E-02 5.40E-02
Thyroid cancer 2D10 Thyroid 2.44E-01 -2.68E-02 -1.49E-01
Tibial muscular dystrophy 8C75 Muscle tissue 3.29E-03 -1.81E-01 -1.28E+00
Tuberous sclerosis complex LD2D.2 Perituberal tissue 2.38E-01 8.17E-02 4.02E-01
Type 2 diabetes 5A11 Liver tissue 6.25E-01 3.58E-01 1.05E+00
Ureter cancer 2C92 Urothelium 2.36E-01 3.28E-02 1.29E-01
Uterine cancer 2C78 Endometrium tissue 6.24E-01 4.53E-02 3.73E-02
Vitiligo ED63.0 Skin 5.76E-02 -7.45E-01 -1.40E+00
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⏷ Show the Full List of DME Expression Under 107 Diseases

References

1 In vitro metabolism study of buprenorphine: evidence for new metabolic pathways. Drug Metab Dispos. 2005 May;33(5):689-95.
2 In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86.
3 Contribution of human hepatic cytochrome p450 isoforms to the metabolism of psychotropic drugs. Biol Pharm Bull. 2005 Sep;28(9):1711-6.
4 Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos. 1999 Jun;27(6):655-66.
5 CYP2C8/9 mediate dapsone N-hydroxylation at clinical concentrations of dapsone. Drug Metab Dispos. 2000 Aug;28(8):865-8.
6 Targeted antipeptide antibodies to cytochrome P450 2C18 based on epitope mapping of an inhibitory monoclonal antibody to P450 2C51. Arch Biochem Biophys. 1997 Feb 15;338(2):157-64.
7 Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
8 Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. J Pharmacol Exp Ther. 1997 Jun;281(3):1199-210.
9 Effects of rifampin on the pharmacokinetics of a single dose of istradefylline in healthy subjects. J Clin Pharmacol. 2018 Feb;58(2):193-201.
10 Oxidative metabolism of lansoprazole by human liver cytochromes P450. Mol Pharmacol. 1995 Feb;47(2):410-8.
11 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
12 Cytochrome P450 metabolic dealkylation of nine N-nitrosodialkylamines by human liver microsomes. Carcinogenesis. 1996 Sep;17(9):2029-34.
13 Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes. Chem Res Toxicol. 1996 Mar;9(2):365-73.
14 Human CYP2C19 is a major omeprazole 5-hydroxylase, as demonstrated with recombinant cytochrome P450 enzymes. Drug Metab Dispos. 1996 Oct;24(10):1081-7.
15 Identification of the human cytochrome P450 isoforms mediating in vitro N-dealkylation of perphenazine. Br J Clin Pharmacol. 2000 Dec;50(6):563-71.
16 Induction of CYP2C genes in human hepatocytes in primary culture. Drug Metab Dispos. 2001 Mar;29(3):242-51.
17 Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
18 Thalidomide metabolism by the CYP2C subfamily. Clin Cancer Res. 2002 Jun;8(6):1964-73.
19 Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8.
20 Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74.
21 Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N-demethylation of aminopyrine. Xenobiotica. 1999 Feb;29(2):187-93.
22 Etizolam (INN) Pre-Review Report.
23 Evaluation of the transport, in vitro metabolism and pharmacokinetics of Salvinorin A, a potent hallucinogen. Eur J Pharm Biopharm. 2009 Jun;72(2):471-7.
24 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.