Enzyme Explorer

Xenobiotics


Enzymes for Multi-Drug Resistance Research

Review Article:
Cytochrome P450 and Related Enzymes

The hepatic microsomal cytochrome P450s are members of a superfamily of monoxygenases that catalyze the oxidative metabolism of xenobiotics, the initial step in the biotransformation and elimination of a wide variety of drugs and environmental pollutants. P450s are located primarily in the endoplasmic reticulum of liver tissue. Until now the difficulty of isolating and reconstituting native enzymes from human tissue has hampered their use for studies with well-defined in vitro drug metabolism systems.

Applications
  • Isozyme identification
  • Determination of kinetic parameters for substrates and inhibitors
  • Isolation and synthesis of rare and novel metabolites
  • Stereo- and/or regio-specific hydroxylation reactions
  • High-throughput in vitro screening

Hepatic microsomal cytochrome P450, human recombinant, was expressed in over producing E. coli.


Product Number Product Description
C3735 Cytochrome P450 1A1 Isozyme, microsomes, human
C7803 Cytochrome P450 1A2 Isozyme, human
C6107 Cytochrome P450 1A2 Isozyme, microsomes, human
C3860 Cytochrome P450 1B1 Isozyme, microsomes, human
C3985 Cytochrome P450 2A6 Isozyme, microsomes, human
C4735 Cytochrome P450 2A6 Isozyme, microsomes, human, with cytochrome with b5
C7552 Cytochrome P450 2B4, from rabbit liver
C3360 Cytochrome P450 2B6 Isozyme, microsomes, human
C4860 Cytochrome P450 2B6 Isozyme, microsomes, human with cytochrome with b5
C4110 Cytochrome P450 2C8 Isozyme, microsomes, human
C3485 Cytochrome P450 2C8 Isozyme, microsomes, human, with cytochrome with b5
C7817 Cytochrome P450 2C9 Isozyme, human
C5107 Cytochrome P450 2C9 Isozyme, microsomes, human
C4235 Cytochrome P450 2C92 Isozyme, microsomes, human
C4360 Cytochrome P450 2C93 Isozyme, microsomes, human
C4485 Cytochrome P450 2C18 Isozyme, microsomes, human
C5607 Cytochrome P450 2C19 Isozyme, human
C4857 Cytochrome P450 2C19 Isozyme, microsomes, human
C9195 Cytochrome P450 2D6 Isozyme, human
C5232 Cytochrome P450 2D6 Isozyme, microsomes, human
C9573 Cytochrome P450 2E1 Isozyme, human
C4982 Cytochrome P450 3A4 Isozyme, microsomes, human
C3831 Cytochrome P450 3A4 Isozyme, human
C6232 Cytochrome P450 3A5 Isozyme, microsomes, human
C3610 Cytochrome P450 3A7 Isozyme, microsomes, human, with cytochrome b5
C4610 Cytochrome P450 4A11 Isozyme, microsomes, human
C4985 Cytochrome P450 4F2 Isozyme, microsomes, human, with cytochrome b5
C5110 Cytochrome P450 4F3A Isozyme, microsomes, human, with cytochrome b5
C5235 Cytochrome P450 4F3B Isozyme, microsomes, human, with cytochrome b5
C5357 Cytochrome P450 Isozyme control, microsomes, human


Hepatic microsomal cytochrome P450 2B4 from rabbit liver was induced with phenobarbital.


Product Number Product Description
C7552 Cytochrome P450 Isozyme 2B4

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Cytochrome-P450 reductase transfers electrons from NADPH to the various isoforms of cytochrome P450. It is a membrane-bound flavoprotein containing one mole each of FAD and FMN. Sigma offers two product options. Sigma's human Cytochrome-P450 reductase is produced from insect cells infected with baculovirus containing the cDNA for human P450 reductase.Sigma's nonrecombinant version is isolated from rabbit liver induced with phenobarbital.


Product Number Product Description
N5516 NADPH-P450 Reductase, Human Recombinant
C4839 NADPH-P450 Reductase, Rabbit

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Cytochrome b5 is a membrane-bound hemoprotein that enhances the catalytic efficiency of some P450 isoforms. Sigma's human cytochrome b5 is overexpressed in E. coli and purified to homogeneity.


Product Number Product Description
C1427 Cytochrome b5

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Five allelic variants of sulfotransferase enzymes are offered for sudies involving drug disposition research. Sigma's highly active cytosolic extracts are produced from insect cells that are infected with a baculovirus containing a cDNA for human sulfotransferases.


Product Number Product Description
S1677 Sulfotransferase 1A12 Isozyme, human, cytosol extract
S8928 Sulfotransferase 1A21 Isozyme, human, cytosol extract
S6054 Sulfotransferase 1A3 Isozyme, human, cytosol extract
S8309 Sulfotransferase 1E Isozyme, human, cytosol extract
S8434 Sulfotransferase 2A1 Isozyme, human, cytosol extract
S7188 Sulfotransferase SF9 wild type control, human, cytosol extract

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Glutathione transferases (GSTs) catalyze the formation of thioether conjugates between glutathione and xenobiotic compounds. Their major biological function is believed to be defense against electrophilic chemical species, many of which are formed by cellular oxidative reactions catalyzed by cytochrome P450 and other oxidases. Sigma's recombinant human GSTs are over-expressed in E. coli and purified by affinity chromatography.


Product Number Product Description
G5524 Glutathione S-Transferase A1-1 Isozyme, human
G4151 Glutathione S-Transferase M1-1 Isozyme, human
G1902 Glutathione S-Transferase P1-1 Isozyme, human
G4385 Glutathione S-Transferase from bovine liver
G6511 Glutathione S-Transferase from equine liver
G6636 Glutathione S-Transferase from porcine liver
G5663 Glutathione S-Transferase from Schistosoma japonicum

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Examining the glucuronidation reactions catalyzed by the human UDP-glycosyltransferase (UGT) family of enzymes is essential when investigating the metabolic fate of any new drug, therapeutic agent, or chemical present in the environment. Sigma's human UDP-glycosyltransferases are produced as a microsomal fractions of Sf-9 insect cells infected with a baculovirus strain containing cDNA for a specific human UGT.


Product Number Product Description
U7254 UDP-Glucuronosyltransferase 1A1 Isozyme, microsomes, human
U8379 UDP-Glucuronosyltransferase 1A3 Isozyme, microsomes, human
U7379 UDP-Glucuronosyltransferase 1A6 Isozyme, microsomes, human
U7504 UDP-Glucuronosyltransferase 1A7 Isozyme, microsomes, human
U7629 UDP-Glucuronosyltransferase 1A10 Isozyme, microsomes, human
U8504 UDP-Glucuronosyltransferase 2B7 Isozyme, microsomes, human
U8007 UDP-Glucuronosyltransferase SF9 Wild type control, microsomes


Cytochrome P450 Fluorescent Detection Kits. With these kits, you can extract samples and assay them for either cytochrome P450 2B4 or P450 1A1/2 activity.Kits contain sufficient reagents for extraction of up to 7.5 g of tissue and up to 50 assays. Ethoxyresorufin and methoxyresorufin are supplied as substrates.


Product Number Product Description
Cyto-1A Cytochrome P450 1A1/2 Activity Kit
Cyto-2B Cytochrome P450 2B Activity Kit

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Substrates


Product Number Product Description Function
A6636 Aflatoxin B1 CYP1A2, CYP2A6, CYP2D6, and CYP3A family substrate
A8423 Amiodarone Hydrochloride CYP2C8/9 and CYP3A family (minor pathway) inhibitor and substrate; CYP2D6, CYP3A family, CYP2D6, CYP2A6, CYP2B6 desethyl-form inhibitor
B5057 7-Benzyloxy-4-Trifluoromethylcoumarin P450 substrate
B5182 7-Benzyloxyquinoline (BQ) P450 substrate
B1532 7-Benzyloxyresorufin P450 substrate
C8138 Chlorpromazine Hydrochloride CYP1A1, CYP2D6, Gluc1A3, Gluc1A4 substrate
C4397 Chlorzoxazone CYP1A2, CYP2E1, and CYP3A family substrate
C6305 Clozapine CYP1A2, CYP2C19, CYP2D6, CYP2A6, CYP3A family, Gluc1A4, Gluc1A3, Gluc1A4 (desmethoxy metabolite only) substrate
D1306 Debrisoquine Sulfate P450, CYP2D6 Substrate
D1756 Dexamethasone CYP2A6, CYP3A and Gluc1 family substrate
D2531 Dextromethorphan Hydrobromide CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A family substrate
D6899 Diclofenac Sodium CYP8/9 inhibitor and substrate; CYP2C19, CYP2B6, Gluc2B7, Gluc1A3, Gluc1A9, CYP3A family substrate; Gluc2B9 and Gluc2B7 inducer
D5878 Digitoxin CYP3A family substrate
D6003 Digoxin CYP3A family substrate (minor pathway)
D2521 Diltiazem Hydrochloride CYP2C8, CYP2C9, CYP3A family substrate
D4505 5,5-Diphenylhydantoin Sodium (Phenytoin) CYP2C8, CYP2C9, CYP2C19, Gluc2B15 substrate; CYP2B6, Gluc1, Gluc2, and CYP3A family inducer
D4035 Doxorubicine Hydrochloride with extender and preservative CYP2D6 and CYP3A family inhibitor and substrate
E3763 Ethoxyresorufin P450 substrate
E1383 Etopsoside Cell cycle inhibitor; CYP3A family substrate; CYP1A2 and CYP2E1 (minor pathway) substrate
F9261 Flunitrazepam CYP2C19 substrate; CYP3A inhibitor or substrate; Gluc2B7 inducer
F132 Fluoxetine Hydrochloride CYP2C8/9, CYP2D6, CYP3A family substrate and inhibitor; CYP1A2 and CYP2B6 inhibitor (includes active metabolites)
G9659 GBR-12935 Dihydrochloride P450 substrate
G4251 Glutathione Free Acid Reduced CYP2E1 substrate, known to be transported by MRP
H1512 Haloperidol CYP2D6 inhibitor and substrate; UGT and CYP3A family substrate
H4001 Hydrocortisone CYP3A family inducer and substrate
I7378 Indomethacin CYP2C19 inducer and substrate; CYP2C8/9 substrate; possible Gluc2B7 inducer
I3377 Isonicotinic Acid Hydrazine Free Base (Isoniazid) CYP2C19 substrate
K1003 Ketoconazole CYP3A family inhibitor and substrate; CYP1A2, CYP2C19, and CYP2A6 inhibitor
L1026 Lidocaine CYP1A2 inhibitor and substrate; CYP2B6 and CYP3A family substrate
M8189 7-Methoxy-4-Trifluoromethylcourmarin P450 substrate
M1544 Methoxyresorufin P450 substrate
M2147 Mevinolin (Lovastatin) CYP2C8/9 inhibitor; CYP2C8/9 and CYP3A family substrate (metabolite)
N7510 Nicardipine Hydrochloride CYP3A family substrate and inhibitor; CYP2C8/9, CYP2C19, CYP2D6 inhibitor
N7634 Nifedipine CYP3A family substrate and inhibitor; CYP2C8/9 inhibitor
N144 Nitrendipine CYP3A family substrate
O104 Omeprazole CYP2C19 and CYP3A family substrate and inhibitor; CYP2C8/9 inhibitor, CYP2C19 substrate (R- form)
T1912 Paclitaxel from Taxus Yannanensis CYP2C8/9 substrate; CYP3A family inducer and substrate
P0928 7-Pentoxyresorufin (O7 Pentylresorufin) P450 substrate
A2500 Phenacetin (Acetophenetidin) P450, CYP1A2, 2C9, 2C19, 2D6 Substrate
P1294 1,10-Phenanthroline Monohydrate P450 substrate
P5178 Phenobarbital Sodium CYP2C19 substrate; CYP2C8/9, CYP1A2, CYP2D6, CYP2A6, CYP2B6, CYP3A, Gluc1, Gluc2 family inducer
P8386 Phenylbutazone CYP2C8/9 inhibitor; CYP3A family inducer
P9391 Procainamide Hydrochloride CYP2D6 substrate; NAT2-selective substrate
P0130 Progesterone CYP2C8/9, CYP2C19, CYP3A family substrate; Pgp inhibitor
Q0750 Quinidine Hydrochloride CYP3A family substrate and inhibitor; CYP2D6 inhibitor; CYP2C8/9 and CYP2E1 substrate
R101 Ranitidine Hydrochloride CYP1A2, CYP2C19, CYP2D6 substrate; possible Gluc2 inducer; FMO substrate
R0395 Rapamycin (Sirolimus) CYP3A family substrate
T5648 Tamoxifen CYP2C8/9, CYP2D6, CYP2E1, CYP3A family substrate
T9652 Terfenadine CYP3A family substrate; Pgp inhibitor
T1500 Testosterone CYP2D6 and possible CYP3A family substrate
T0891 Tolbutamide CYP2C8/9, CYP2C19 substrate
P1761 trans-2-Phenylcyclopropylamine Hemisulfate (Tranylcypromine) CYP2C19, CYP2E1, CYP2A6 inhibitor; MAO substrate
T6154 Trazodone Hydrochloride CYP3A family substrate; CYP2D6 substrate (metabolite)
T8516 Trifluoroperazine Dihydrochloride CYP1A2 (minor pathway) substrate; Gluc1A4 substrate; Pgp inhibitor
V4629 (+-)- Verapamil Hydrochloride CYP3A family inhibitor and substrate; CYP1A2, CYP2C8/9, CYP2C19 (minor pathway) substrate; Pgp inhibitor
V1377 Vinblastine Sulfate CYP2D6 inhibitor and substrate; CYP3A family substrate; Pgp substrate
V8879 Vincristine Sulfate CYP3A family substrate; Pgp inducer
A2250 Warfarin CYP2C8 and CYP2C9 S-form substrate; 1A2 R-form substrate; R-form may inhibit CYP2C9
C8138 Chlorpromazine Hydrochloride CYP1A1, CYP2D6, Gluc1A3, Gluc1A4 substrate
C6305 Clozapine CYP1A2, CYP2C19, CYP2D6, CYP2A6, CYP3A family, Gluc1A4, Gluc1A3, Gluc1A4 (desmethoxy metabolite only) substrate
D1756 Dexamethasone CYP2A6, CYP3A and Gluc1 family substrate
D6899 Diclofenac Sodium CYP8/9 inhibitor and substrate; CYP2C19, CYP2B6, Gluc2B7, Gluc1A3, Gluc1A9, CYP3A family substrate; Gluc2B9 and Gluc2B7 inducer
D4505 5,5-Diphenylhydantoin Sodium (Phenytoin) CYP2C8, CYP2C9, CYP2C19, Gluc2B15 substrate; CYP2B6, Gluc1, Gluc 2, and CYP3A family inducer
T8516 Trifluoroperazine Dihydrochloride CYP1A2 substrate (minor pathway); Gluc1A4 substrate; Pgp inhibitor

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Inhibitors


Product Number Product Description Function
A8423 Amiodarone Hydrochloride CYP2C8/9 and CYP3A family (minor pathway) inhibitor and substrate; CYP2D6, CYP3A family, CYP2D6, CYP2A6, CYP2B6 desethyl-form inhibitor
C4522 Cimetidine CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A family inhibitor
D6899 Diclofenac Sodium CYP8/9 inhibitor and substrate; CYP2C19, CYP2B6, Gluc2B7, Gluc1A3, Gluc1A9, CYP3A family substrate; Gluc2B9 and Gluc2B7 inducer
D4035 Doxorubicine Hydrochloride with extender and preservative CYP2D6 and CYP3A family inhibitor and substrate
E3764 Enoxacin CYP1A2 and CYP3A family inhibitor
E8875 B-Estradiol CYP1A2 inhibitor
F132 Fluoxetine Hydrochloride CYP2C8/9CYP2D6, CYP3A family substrate and inhibitor; CYP1A2 and CYP2B6 inhibitor (includes active metabolites)
F4765 Fluphenazine Dihydrochloride CYP1A2 and CYP2D6 inhibitor
F124 Furafylline CYP1A2 inhibitor
H1512 Haloperidol CYP2D6 inhibitor and substrate; UGT and CYP3A family substrate
H8885 Hydroxyzine Dihydrochloride CYP2D6 inhibitor
K1003 Ketoconazole CYP3A family inhibitor and substrate; CYP1A2, CYP2C19, and CYP2A6 inhibitor
L1026 Lidocaine CYP1A2 inhibitor and substrate; CYP2B6 and CYP3A family substrate
M2147 Mevinolin (Lovastatin) CYP2C8/9 inhibitor; CYP2C8/9 and CYP3A family substrate (metabolite)
N7510 Nicardipine Hydrochloride CYP3A family substrate and inhibitor; CYP2C8/9, CYP2C19, CYP2D6 inhibitor
N7634 Nifedipine CYP3A family substrate and inhibitor; CYP2C8/9 inhibitor
O8757 Ofloxacin CYP1A2 inhibitor
O104 Omeprazole CYP2C19 and CYP3A family substrate and inhibitor; CYP2C8/9 inhibitor; CYP2C19 substrate (R- form)
P8761 Probenecid CYP2C19 and Gluc2 inhibitor
P6273 2-Propylpentanoic Acid (Valproic acid) P450 inhibitor
Q0750 Quinidine Hydrochloride CYP3A family substrate and inhibitor; CYP2D6 inhibitor; CYP2C8/9 and CYP2E1 substrate
S0758 Sulfaphenazole P450 enzyme-selective inhibitor
S9509 (-+)-Sulfinpyrazone CYP2C8/9 inhibitor; CYP3A family inducer; MDR modulating compound
P1761 trans-2-Phenylcyclopropylamine Hemisufate (Tranylcypromine) CYP2C19, CYP2E1, CYP2A6 inhibitor; MAO substrate
V4629 (+-)- Verapamil Hydrochloride CYP3A family inhibitor and substrate; CYP1A2, CYP2C8/9, CYP2C19 (minor pathway) substrate; Pgp inhibitor
V1377 Vinblastine Sulfate CYP2D6 inhibitor and substrate; CYP3A family substrate; Pgp substrate
P8761 Probenecid CYP2C19 and Gluc2 inhibitor

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