cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10)

Function: 1) NADPH-dependent electron transport pathway 2) oxidizes a variety of structurally unrelated compounds - steroids, fatty acids, xenobiotics 3) the S isoform of warfarin is a substrate of cyt P450 2C9 the R isoform of limonene is a substrate of cyt P450 2C9 4) inducers - aprepitant - carbamazepine - nilotinib - phenobarbital - phenytoin - primidone - rifampin - rifapentine - ritonavir - Hypericum perforatum (St John's wort) 5) inhibitors - amiodarone - cotrimoxazole - delavirdine - efavirenz - etravirine - fenofibrate - fluconazole - fluorouracil - fluoxetine - fluvastatin - fluvoxamine - gemfibrozil - Gingko biloba - imatinib - isoniazid - itraconazole - ketoconazole - leflunomide - lovastatin - Lycium barbarum - metronidazole - milk thistle - modafinil - oxandrolone - omeprazole - paroxetine - sertraline - sulfamethoxazole - ticlopidine - Vaccinium_macrocarpon (cranberry) - voriconazole - zafirlukast 6) substrates - amitriptyline - carvedilol - celecoxib - clomipramine - desogestrel - diazepam - diclofenac - dronabinol - etravirine - fluoxetine - flurbiprofen - fluvastatin - formoterol - glimepiride - glipizide - glyburide - ibuprofen - imipramine - indomethacin - irbesartan - losartan - mefenamic acid - meloxicam - methadone - montelukast - naproxen - nateglinide - omeprazole - phenytoin - piroxicam - ramelteon - rosiglitazone - sildenafil - sulfamethoxazole - tamoxifen - tolbutamide - torsemide - valdecoxib - valsartan - vardenafil - voriconazole - warfarin - zafirlukast - zileuton Inhibition: - among the inhibitors of cyt P450 2C9, fluvoxamine is a strong inhibitor & ketoconazole is a weak inhibitor Compartment: membrane-bound, endoplasmic reticulum Expression: rifampin is a strong inducer Pathology: - CYP2C9 alleles are associated with warfarin resistance Laboratory: - CYP2C9 allele 2 - CYP2C9 allele 3 - CYP2C9 gene mutation

Related

cyt P450 2C9 gene warfarin sensitivity testing (CYP2C8, CYP2C9, CYP4F2, VKORC1)

Properties

SIZE: MW = 56 kD entity length = 490 aa COMPARTMENT: endoplasmic reticulum MOTIF: Iron [Fe]-binding site SITE: 435-435 SUBSTRATE: amitriptyline carvedilol celecoxib clomipramine desogestrel diazepam diclofenac dronabinol etravirine fluoxetine flurbiprofen fluvastatin formoterol glimepiride glipizide glyburide ibuprofen imipramine indomethacin irbesartan losartan mefenamate meloxicam methadone montelukast naproxen nateglinide omeprazole phenytoin piroxicam ramelteon rosiglitazone sildenafil sulfamethoxazole tamoxifen tolbutamide torsemide valdecoxib valsartan vardenafil voriconazole warfarin zafirlukast zileuton INDUCERS: aprepitant carbamazepine nilotinib phenobarbital phenytoin primidone rifampin rifapentine ritonavir Hypericum perforatum INHIBITORS: amiodarone Cannabis sativa (hemp, marijuana, pot, grass) trimethoprim/sulfamethoxazole delavirdine efavirenz etravirine fenofibrate fluconazole 5-fluorouracil fluoxetine fluvastatin fluvoxamine gemfibrozil Ginkgo biloba imatinib isoniazid ketoconazole leflunomide lovastatin Goji metronidazole milk thistle modafinil nilotinib oxandrolone omeprazole paroxetine Piper methysticum (Kava-Kava) sertraline sulfamethoxazole ticlopidine Vaccinium macrocarpon (Cranberry) voriconazole zafirlukast

Database Correlations

OMIM 601130 UniProt P11712 Pfam PF00067 Entrez Gene 1559 Kegg hsa:1559 ENZYME correlations