سیتوکروم P450 خانواده ۲ زیرخانواده C عضو ۹ (به اختصار CYP2C9) یک پروتئین آنزیمی است. این آنزیم در متابولیسم بیگانهزیستها، از جمله داروها و ترکیبات درونزا (مانند اسیدهای چرب) از طریق اکسایش نقش دارد. این پروتئین در انسان توسط ژن CYP2C9 کدگذاری می شود.[4][5] این ژن بسیار چند ریخت است که بر بازدهی متابولیسم توسط آنزیم تأثیر می گذارد.[6]
اطلاعات اجمالی ساختارهای موجود, PDB ...
بستن
اطلاعات بیشتر سوبستراها, مهارکنندهها ...
برخی سوبستراها، مهارکنندهها و القاکنندههای CYP2C9
سوبستراها | مهارکنندهها | القاکنندهها |
|
قوی
ملایم
ضعیف
قدرت نامشخص
|
قوی
ضعیف
|
بستن
Romkes M, Faletto MB, Blaisdell JA, Raucy JL, Goldstein JA (April 1991). "Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily". Biochemistry. 30 (13): 3247–55. doi:10.1021/bi00227a012. PMID 2009263. "CYP2C9". National Center for Biotechnology Information, U.S. National Library of Medicine. 29 March 2021. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by rifampin. The enzyme is known to metabolize many xenobiotics, including phenytoin, tolbutamide, ibuprofen and S-warfarin. Studies identifying individuals who are poor metabolizers of phenytoin and tolbutamide suggest that this gene is polymorphic. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24.
Guo Y, Zhang Y, Wang Y, Chen X, Si D, Zhong D, Fawcett JP, Zhou H (June 2005). "Role of CYP2C9 and its variants (CYP2C9*3 and CYP2C9*13) in the metabolism of lornoxicam in humans". Drug Metabolism and Disposition. 33 (6): 749–53. doi:10.1124/dmd.105.003616. PMID 15764711. S2CID 24199800. Abdullah Alkattan & Eman Alsalameen (2021) Polymorphisms of genes related to phase-I metabolic enzymes affecting the clinical efficacy and safety of clopidogrel treatment, Expert Opinion on Drug Metabolism & Toxicology, DOI: 10.1080/17425255.2021.1925249
Bland TM, Haining RL, Tracy TS, Callery PS (October 2005). "CYP2C-catalyzed delta9-tetrahydrocannabinol metabolism: kinetics, pharmacogenetics and interaction with phenytoin". Biochemical Pharmacology. 70 (7): 1096–103. doi:10.1016/j.bcp.2005.07.007. PMID 16112652. Miyazawa M, Shindo M, Shimada T (May 2002). "Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes". Drug Metabolism and Disposition. 30 (5): 602–7. doi:10.1124/dmd.30.5.602. PMID 11950794. Kosuge K, Jun Y, Watanabe H, Kimura M, Nishimoto M, Ishizaki T, Ohashi K (October 2001). "Effects of CYP3A4 inhibition by diltiazem on pharmacokinetics and dynamics of diazepam in relation to CYP2C19 genotype status". Drug Metabolism and Disposition. 29 (10): 1284–9. PMID 11560871. Kimura Y, Ito H, Ohnishi R, Hatano T (Jan 2010). "Inhibitory effects of polyphenols on human cytochrome P450 3A4 and 2C9 activity". Food and Chemical Toxicology. 48 (1): 429–35. doi:10.1016/j.fct.2009.10.041. PMID 19883715. Pan X, Tan N, Zeng G, Zhang Y, Jia R (October 2005). "Amentoflavone and its derivatives as novel natural inhibitors of human Cathepsin B". Bioorganic & Medicinal Chemistry. 13 (20): 5819–25. doi:10.1016/j.bmc.2005.05.071. PMID 16084098. Kudo T, Endo Y, Taguchi R, Yatsu M, Ito K (May 2015). "Metronidazole reduces the expression of cytochrome P450 enzymes in HepaRG cells and cryopreserved human hepatocytes". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 45 (5): 413–419. doi:10.3109/00498254.2014.990948. PMID 25470432. S2CID 26910995. Tirkkonen T, Heikkilä P, Huupponen R, Laine K (October 2010). "Potential CYP2C9-mediated drug-drug interactions in hospitalized type 2 diabetes mellitus patients treated with the sulphonylureas glibenclamide, glimepiride or glipizide". Journal of Internal Medicine. 268 (4): 359–366. doi:10.1111/j.1365-2796.2010.02257.x. PMID 20698928. S2CID 45449460. Robertson P, DeCory HH, Madan A, Parkinson A (June 2000). "In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil". Drug Metabolism and Disposition. 28 (6): 664–71. PMID 10820139. Yamaori S, Koeda K, Kushihara M, Hada Y, Yamamoto I, Watanabe K (2012-01-01). "Comparison in the in vitro inhibitory effects of major phytocannabinoids and polycyclic aromatic hydrocarbons contained in marijuana smoke on cytochrome P450 2C9 activity". Drug Metabolism and Pharmacokinetics. 27 (3): 294–300. doi:10.2133/dmpk.DMPK-11-RG-107. PMID 22166891.
- Goldstein JA, de Morais SM (December 1994). "Biochemistry and molecular biology of the human CYP2C subfamily". Pharmacogenetics. 4 (6): 285–99. doi:10.1097/00008571-199412000-00001. PMID 7704034.
- Miners JO, Birkett DJ (June 1998). "Cytochrome P4502C9: an enzyme of major importance in human drug metabolism". British Journal of Clinical Pharmacology. 45 (6): 525–38. doi:10.1046/j.1365-2125.1998.00721.x. PMC 1873650. PMID 9663807.
- Smith G, Stubbins MJ, Harries LW, Wolf CR (December 1998). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica. 28 (12): 1129–65. doi:10.1080/004982598238868. PMID 9890157.
- Henderson RF (June 2001). "Species differences in the metabolism of olefins: implications for risk assessment". Chemico-Biological Interactions. 135–136: 53–64. doi:10.1016/S0009-2797(01)00170-3. PMID 11397381.
- Xie HG, Prasad HC, Kim RB, Stein CM (November 2002). "CYP2C9 allelic variants: ethnic distribution and functional significance". Advanced Drug Delivery Reviews. 54 (10): 1257–70. doi:10.1016/S0169-409X(02)00076-5. PMID 12406644.
- Palkimas MP, Skinner HM, Gandhi PJ, Gardner AJ (June 2003). "Polymorphism induced sensitivity to warfarin: a review of the literature". Journal of Thrombosis and Thrombolysis. 15 (3): 205–12. doi:10.1023/B:THRO.0000011376.12309.af. PMID 14739630. S2CID 20497247.
- Daly AK, Aithal GP (August 2003). "Genetic regulation of warfarin metabolism and response". Seminars in Vascular Medicine. 3 (3): 231–8. doi:10.1055/s-2003-44458. PMID 15199455.