Molecule Information

General Information of the Molecule (ID: Mol01861)

• Name: Cytochrome P450 family 2 subfamily C member 9 (CYP2C9) ,Homo sapiens
• Synonyms: CYP2C9; CYP2C10
• Molecule Type: Protein
• Gene Name: CYP2C9
• Gene ID: 1559
• Location: chr10:94,938,658-94,990,091[+]
• Sequence:
  MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV
  YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW
  KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
  IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM
  KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE
  TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID
  LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK
  KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP
  PFYQLCFIPV
• Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids. 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 epoxidation of double bonds of polyunsaturated fatty acids (PUFA). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis. Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2. Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol. Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
• Uniprot ID: CP2C9_HUMAN
• Ensembl ID: ENSG00000138109
• HGNC ID: HGNC:2623

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Celecoxib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Dysmenorrhea [1]

• Resistant Disease: Dysmenorrhea [ICD-11: GA34.3]
• Resistant Drug: Celecoxib
• Molecule Alteration: SNP; CYP2C9*2/*2
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: For example, the CYP2C9*2/*2 polymorphism was associated with increased total clearance of celecoxib and diclofenac.48 More research is necessary to determine if other gain-of-function variants exist and alter NSAID metabolism.

Clopidogrel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Hypo-attenuated leaflet thickening [2]

• Resistant Disease: Hypo-attenuated leaflet thickening [ICD-11: BD10.2]
• Resistant Drug: Clopidogrel
• Molecule Alteration: SNP; rs1799853+rs1057910
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: We thoroughly genotyped 34 SNPs and 8 SNPs that have been reported for clopidogrel and aspirin resistance. A total of 148 patients were enrolled. There were 15 patients demonstrating signs of HALT. Patients with HALT had a higher rate of atrial fibrillation (AF) pre-TAVR (33.3 vs. 7.5%, P = 0.01).

Diclofenac

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Dysmenorrhea [1]

• Resistant Disease: Dysmenorrhea [ICD-11: GA34.3]
• Resistant Drug: Diclofenac
• Molecule Alteration: SNP; CYP2C9*2/*2
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: For example, the CYP2C9*2/*2 polymorphism was associated with increased total clearance of celecoxib and diclofenac.48 More research is necessary to determine if other gain-of-function variants exist and alter NSAID metabolism.

References

• Ref 1: Nonsteroidal antiinflammatory drug resistance in dysmenorrhea: epidemiology, causes, and treatment .Am J Obstet Gynecol. 2018 Apr;218(4):390-400. doi: 10.1016/j.ajog.2017.08.108. Epub 2017 Sep 6. 10.1016/j.ajog.2017.08.108
• Ref 2: Gene polymorphisms in dual antiplatelet therapy and the presence of hypo-attenuated leaflet thickening after transcatheter aortic valve replacement .J Thromb Thrombolysis. 2018 Apr;45(3):463-465. doi: 10.1007/s11239-018-1636-z. 10.1007/s11239-018-1636-z