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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
C 3735 Cytochrome P450 1A1 Isozyme, microsomes, human
C 7803 Cytochrome P450 1A2 Isozyme, human
C 6107 Cytochrome P450 1A2 Isozyme, microsomes, human
C 3860 Cytochrome P450 1B1 Isozyme, microsomes, human
C 3985 Cytochrome P450 2A6 Isozyme, microsomes, human
C 4735 Cytochrome P450 2A6 Isozyme, microsomes, human, with cytochrome with b5
C 7552 Cytochrome P450 2B4, from rabbit liver
C 3360 Cytochrome P450 2B6 Isozyme, microsomes, human
C 4860 Cytochrome P450 2B6 Isozyme, microsomes, human with cytochrome with b5
C 4110 Cytochrome P450 2C8 Isozyme, microsomes, human
C 3485 Cytochrome P450 2C8 Isozyme, microsomes, human, with cytochrome with b5
C 7817 Cytochrome P450 2C9 Isozyme, human
C 5107 Cytochrome P450 2C9 Isozyme, microsomes, human
C 4235 Cytochrome P450 2C92 Isozyme, microsomes, human
C 4360 Cytochrome P450 2C93 Isozyme, microsomes, human
C 4485 Cytochrome P450 2C18 Isozyme, microsomes, human
C 5607 Cytochrome P450 2C19 Isozyme, human
C 4857 Cytochrome P450 2C19 Isozyme, microsomes, human
C 9195 Cytochrome P450 2D6 Isozyme, human
C 5232 Cytochrome P450 2D6 Isozyme, microsomes, human
C 9573 Cytochrome P450 2E1 Isozyme, human
C 4982 Cytochrome P450 3A4 Isozyme, microsomes, human
C 3831 Cytochrome P450 3A4 Isozyme, human
C 6232 Cytochrome P450 3A5 Isozyme, microsomes, human
C Cytochrome P450 3A7 Isozyme, microsomes, human, with cytochrome b5
C 4610 Cytochrome P450 4A11 Isozyme, microsomes, human
C 4985 Cytochrome P450 4F2 Isozyme, microsomes, human, with cytochrome b5
C 5110 Cytochrome P450 4F3A Isozyme, microsomes, human, with cytochrome b5
C 5235 Cytochrome P450 4F3B Isozyme, microsomes, human, with cytochrome b5
C 5357 Cytochrome P450 Isozyme control, microsomes, human


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


Product Number Product Description
C 7552 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
N 5516 NADPH-P450 Reductase, Human Recombinant
C 4839 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
C 1427 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
S 1677 Sulfotransferase 1A12 Isozyme, human, cytosol extract
S 8928 Sulfotransferase 1A21 Isozyme, human, cytosol extract
S 6054 Sulfotransferase 1A3 Isozyme, human, cytosol extract
S 8309 Sulfotransferase 1E Isozyme, human, cytosol extract
S 8434 Sulfotransferase 2A1 Isozyme, human, cytosol extract
S 7188 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
G 5524 Glutathione S-Transferase A1-1 Isozyme, human
G 4151 Glutathione S-Transferase M1-1 Isozyme, human
G 1902 Glutathione S-Transferase P1-1 Isozyme, human
G 4385 Glutathione S-Transferase from bovine liver
G 6511 Glutathione S-Transferase from equine liver
G 6636 Glutathione S-Transferase from porcine liver
G 5663 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
U 7254 UDP-Glucuronosyltransferase 1A1 Isozyme, microsomes, human
U 8379 UDP-Glucuronosyltransferase 1A3 Isozyme, microsomes, human
U 7379 UDP-Glucuronosyltransferase 1A6 Isozyme, microsomes, human
U 7504 UDP-Glucuronosyltransferase 1A7 Isozyme, microsomes, human
U 7629 UDP-Glucuronosyltransferase 1A10 Isozyme, microsomes, human
U 8504 UDP-Glucuronosyltransferase 2B7 Isozyme, microsomes, human
U 8007 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
A 6636 Aflatoxin B1 CYP1A2, CYP2A6, CYP2D6, and CYP3A family substrate
A 8423 Amiodarone Hydrochloride CYP2C8/9 and CYP3A family (minor pathway) inhibitor and substrate; CYP2D6, CYP3A family, CYP2D6, CYP2A6, CYP2B6 desethyl-form inhibitor
B 5057 7-Benzyloxy-4-Trifluoromethylcoumarin P450 substrate
B 5182 7-Benzyloxyquinoline (BQ) P450 substrate
B 1532 7-Benzyloxyresorufin P450 substrate
C 8138 Chlorpromazine Hydrochloride CYP1A1, CYP2D6, Gluc1A3, Gluc1A4 substrate
C 4397 Chlorzoxazone CYP1A2, CYP2E1, and CYP3A family substrate
C 6305 Clozapine CYP1A2, CYP2C19, CYP2D6, CYP2A6, CYP3A family, Gluc1A4, Gluc1A3, Gluc1A4 (desmethoxy metabolite only) substrate
D 1306 Debrisoquine Sulfate P450, CYP2D6 Substrate
D 1756 Dexamethasone CYP2A6, CYP3A and Gluc1 family substrate
D 2531 Dextromethorphan Hydrobromide CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A family substrate
D 6899 Diclofenac Sodium CYP8/9 inhibitor and substrate; CYP2C19, CYP2B6, Gluc2B7, Gluc1A3, Gluc1A9, CYP3A family substrate; Gluc2B9 and Gluc2B7 inducer
D 5878 Digitoxin CYP3A family substrate
D 6003 Digoxin CYP3A family substrate (minor pathway)
D 2521 Diltiazem Hydrochloride CYP2C8, CYP2C9, CYP3A family substrate
D 4505 5,5-Diphenylhydantoin Sodium (Phenytoin) CYP2C8, CYP2C9, CYP2C19, Gluc2B15 substrate; CYP2B6, Gluc1, Gluc2, and CYP3A family inducer
D 4035 Doxorubicine Hydrochloride with extender and preservative CYP2D6 and CYP3A family inhibitor and substrate
E 3763 Ethoxyresorufin P450 substrate
E 1383 Etopsoside Cell cycle inhibitor; CYP3A family substrate; CYP1A2 and CYP2E1 (minor pathway) substrate
F 9261 Flunitrazepam CYP2C19 substrate; CYP3A inhibitor or substrate; Gluc2B7 inducer
F-132 Fluoxetine Hydrochloride CYP2C8/9, CYP2D6, CYP3A family substrate and inhibitor; CYP1A2 and CYP2B6 inhibitor (includes active metabolites)
G 9659 GBR-12935 Dihydrochloride P450 substrate
G 4251 Glutathione Free Acid Reduced CYP2E1 substrate, known to be transported by MRP
H 1512 Haloperidol CYP2D6 inhibitor and substrate; UGT and CYP3A family substrate
H 4001 Hydrocortisone CYP3A family inducer and substrate
I 7378 Indomethacin CYP2C19 inducer and substrate; CYP2C8/9 substrate; possible Gluc2B7 inducer
I 3377 Isonicotinic Acid Hydrazine Free Base (Isoniazid) CYP2C19 substrate
K 1003 Ketoconazole CYP3A family inhibitor and substrate; CYP1A2, CYP2C19, and CYP2A6 inhibitor
L 1026 Lidocaine CYP1A2 inhibitor and substrate; CYP2B6 and CYP3A family substrate
M 8189 7-Methoxy-4-Trifluoromethylcourmarin P450 substrate
M 1544 Methoxyresorufin P450 substrate
M 2147 Mevinolin (Lovastatin) CYP2C8/9 inhibitor; CYP2C8/9 and CYP3A family substrate (metabolite)
N 7510 Nicardipine Hydrochloride CYP3A family substrate and inhibitor; CYP2C8/9, CYP2C19, CYP2D6 inhibitor
N 7634 Nifedipine CYP3A family substrate and inhibitor; CYP2C8/9 inhibitor
N-144 Nitrendipine CYP3A family substrate
O-104 Omeprazole CYP2C19 and CYP3A family substrate and inhibitor; CYP2C8/9 inhibitor, CYP2C19 substrate (R- form)
T 1912 Paclitaxel from Taxus Yannanensis CYP2C8/9 substrate; CYP3A family inducer and substrate
P 0928 7-Pentoxyresorufin (O7 Pentylresorufin) P450 substrate
A 2500 Phenacetin (Acetophenetidin) P450, CYP1A2, 2C9, 2C19, 2D6 Substrate
P 1294 1,10-Phenanthroline Monohydrate P450 substrate
P 5178 Phenobarbital Sodium CYP2C19 substrate; CYP2C8/9, CYP1A2, CYP2D6, CYP2A6, CYP2B6, CYP3A, Gluc1, Gluc2 family inducer
P 8386 Phenylbutazone CYP2C8/9 inhibitor; CYP3A family inducer
P 9391 Procainamide Hydrochloride CYP2D6 substrate; NAT2-selective substrate
P 0130 Progesterone CYP2C8/9, CYP2C19, CYP3A family substrate; Pgp inhibitor
Q 0750 Quinidine Hydrochloride CYP3A family substrate and inhibitor; CYP2D6 inhibitor; CYP2C8/9 and CYP2E1 substrate
R-101 Ranitidine Hydrochloride CYP1A2, CYP2C19, CYP2D6 substrate; possible Gluc2 inducer; FMO substrate
R 0395 Rapamycin (Sirolimus) CYP3A family substrate
T 5648 Tamoxifen CYP2C8/9, CYP2D6, CYP2E1, CYP3A family substrate
T 9652 Terfenadine CYP3A family substrate; Pgp inhibitor
T 1500 Testosterone CYP2D6 and possible CYP3A family substrate
T 0891 Tolbutamide CYP2C8/9, CYP2C19 substrate
P 1761 trans-2-Phenylcyclopropylamine Hemisulfate (Tranylcypromine) CYP2C19, CYP2E1, CYP2A6 inhibitor; MAO substrate
T 6154 Trazodone Hydrochloride CYP3A family substrate; CYP2D6 substrate (metabolite)
T 8516 Trifluoroperazine Dihydrochloride CYP1A2 (minor pathway) substrate; Gluc1A4 substrate; Pgp inhibitor
V 4629 (+-)- Verapamil Hydrochloride CYP3A family inhibitor and substrate; CYP1A2, CYP2C8/9, CYP2C19 (minor pathway) substrate; Pgp inhibitor
V 1377 Vinblastine Sulfate CYP2D6 inhibitor and substrate; CYP3A family substrate; Pgp substrate
V 8879 Vincristine Sulfate CYP3A family substrate; Pgp inducer
A 2250 Warfarin CYP2C8 and CYP2C9 S-form substrate; 1A2 R-form substrate; R-form may inhibit CYP2C9
C 8138 Chlorpromazine Hydrochloride CYP1A1, CYP2D6, Gluc1A3, Gluc1A4 substrate
C 6305 Clozapine CYP1A2, CYP2C19, CYP2D6, CYP2A6, CYP3A family, Gluc1A4, Gluc1A3, Gluc1A4 (desmethoxy metabolite only) substrate
D 1756 Dexamethasone CYP2A6, CYP3A and Gluc1 family substrate
D 6899 Diclofenac Sodium CYP8/9 inhibitor and substrate; CYP2C19, CYP2B6, Gluc2B7, Gluc1A3, Gluc1A9, CYP3A family substrate; Gluc2B9 and Gluc2B7 inducer
D 4505 5,5-Diphenylhydantoin Sodium (Phenytoin) CYP2C8, CYP2C9, CYP2C19, Gluc2B15 substrate; CYP2B6, Gluc1, Gluc 2, and CYP3A family inducer
T 8516 Trifluoroperazine Dihydrochloride CYP1A2 substrate (minor pathway); Gluc1A4 substrate; Pgp inhibitor

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Inhibitors


Product Number Product Description Function
A 8423 Amiodarone Hydrochloride CYP2C8/9 and CYP3A family (minor pathway) inhibitor and substrate; CYP2D6, CYP3A family, CYP2D6, CYP2A6, CYP2B6 desethyl-form inhibitor
C 4522 Cimetidine CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A family inhibitor
D 6899 Diclofenac Sodium CYP8/9 inhibitor and substrate; CYP2C19, CYP2B6, Gluc2B7, Gluc1A3, Gluc1A9, CYP3A family substrate; Gluc2B9 and Gluc2B7 inducer
D 4035 Doxorubicine Hydrochloride with extender and preservative CYP2D6 and CYP3A family inhibitor and substrate
E 3764 Enoxacin CYP1A2 and CYP3A family inhibitor
E 8875 B-Estradiol CYP1A2 inhibitor
F-132 Fluoxetine Hydrochloride CYP2C8/9CYP2D6, CYP3A family substrate and inhibitor; CYP1A2 and CYP2B6 inhibitor (includes active metabolites)
F 4765 Fluphenazine Dihydrochloride CYP1A2 and CYP2D6 inhibitor
F-124 Furafylline CYP1A2 inhibitor
H 1512 Haloperidol CYP2D6 inhibitor and substrate; UGT and CYP3A family substrate
H 8885 Hydroxyzine Dihydrochloride CYP2D6 inhibitor
K 1003 Ketoconazole CYP3A family inhibitor and substrate; CYP1A2, CYP2C19, and CYP2A6 inhibitor
L 1026 Lidocaine CYP1A2 inhibitor and substrate; CYP2B6 and CYP3A family substrate
M 2147 Mevinolin (Lovastatin) CYP2C8/9 inhibitor; CYP2C8/9 and CYP3A family substrate (metabolite)
N 7510 Nicardipine Hydrochloride CYP3A family substrate and inhibitor; CYP2C8/9, CYP2C19, CYP2D6 inhibitor
N 7634 Nifedipine CYP3A family substrate and inhibitor; CYP2C8/9 inhibitor
O 8757 Ofloxacin CYP1A2 inhibitor
O-104 Omeprazole CYP2C19 and CYP3A family substrate and inhibitor; CYP2C8/9 inhibitor; CYP2C19 substrate (R- form)
P 8761 Probenecid CYP2C19 and Gluc2 inhibitor
P 6273 2-Propylpentanoic Acid (Valproic acid) P450 inhibitor
Q 0750 Quinidine Hydrochloride CYP3A family substrate and inhibitor; CYP2D6 inhibitor; CYP2C8/9 and CYP2E1 substrate
S 0758 Sulfaphenazole P450 enzyme-selective inhibitor
S 9509 (-+)-Sulfinpyrazone CYP2C8/9 inhibitor; CYP3A family inducer; MDR modulating compound
P 1761 trans-2-Phenylcyclopropylamine Hemisufate (Tranylcypromine) CYP2C19, CYP2E1, CYP2A6 inhibitor; MAO substrate
V 4629 (+-)- Verapamil Hydrochloride CYP3A family inhibitor and substrate; CYP1A2, CYP2C8/9, CYP2C19 (minor pathway) substrate; Pgp inhibitor
V 1377 Vinblastine Sulfate CYP2D6 inhibitor and substrate; CYP3A family substrate; Pgp substrate
P 8761 Probenecid CYP2C19 and Gluc2 inhibitor

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