Estimation/Inhibition of CYP Species
Estimation of Metabolizing Enzymes
Identification of the drug-metabolizing enzymes under development is considered very important because inter-individual variation due to drug interaction or SNPs should be avoided. We conduct analysis of a variety of enzymes such as CYP, FMO, MAO, UGT and hydrolases. We can design suitable test systems in compliance with various guidelines by combining an expression system, specific inhibitors and antibody. Examinations by various measurement methods such as HPLC with radioactive detection and LC/MS/MS are possible.
Enzyme available in human CYP expression system | Enzyme available in Human UGT expression system | Inhibitor (CYP) | Antibody |
---|---|---|---|
CYP1A1 | UGT1A1 | Anti-humanCYP1A1 | |
CYP1A2 | UGT1A3 | Furafylline | Anti-humanCYP1A2 |
CYP1B1 | UGT1A4 | Anti-humanCYP2A6 | |
CYP2A6 | UGT1A6 | Methoxsalen | Anti-humanCYP2C8 |
CYP2B6 | UGT1A7 | Sertraline | Anti-humanCYP2C9 |
CYP2C8 | UGT1A8 | Quercetine | Anti-humanCYP2C19 |
CYP2C9*1 | UGT1A9 | Sulfaphenazole | Anti-humanCYP2D6 |
CYP2C9*2 | UGT1A10 | Sulfaphenazole | Anti-humanCYP2E1 |
CYP2C0*3 | UGT2B4 | Sulfaphenazole | Anti-humanCYP3A4 |
CYP2C18 | UGT2B7 | ||
CYP2C19 | UGT2B15 | Benzylnirvanol | |
CYP2D6 | UGT2B17 | Quinidine | |
CYP2E1 | DDC | ||
CYP2J2 | |||
CYP3A4 | Ketoconazole | ||
CYP3A5 | |||
CYP4A11 | |||
MAO-A | |||
MAO-B | |||
FMO-1 | |||
FMO-3 | |||
FMO-5 | |||
NAT1 | |||
NAT2 |
Metabolizing enzyme inhibition study
We conduct CYP inhibition studies using human liver microsome to predict drug interaction. The inhibition activity of a test substance is examined using validated metabolic reactions. The IC50 and Ki values are calculated, and the inhibition activity over time is evaluated.
Species | Substance | Metabolite | Inhibitor |
---|---|---|---|
CYP1A2 | Ethoxy resorufin Phenacetin |
Resorufin Acetaminophen |
Furafylline |
CYP2A6 | Coumarin | 7-Hydroxycoumarin | Methoxsalen |
CYP2B6 | S-(+)-Mephenytoin Bupropion |
Nirvanol Hydroxybupropion |
Sertraline Thio TEPA |
CYP2C8 | Paclitaxel Amodiaquin |
6α-Hydroxypaclitaxel | Quercetine Amiodarone |
CYP2C9 | Diclofenac Tolbutamide | 4-Hydroxydiclofenac Hydroxytolbutamide |
Sulfaphenazole Suprofen |
CYP2C19 | S-(+)-Mephenytoin | (±)-4‘-Hydroxymephenytoin | Benzylnirvanol Ticlopidine |
CYP2D6 | (±)-Bufuralol Dextromethorphan | (±)-Hydroxybufuralol Dextrorphan | Quinidine Paroxetine |
CYP2E1 | Chlorzoxazone | 6-Hydroxychlorzoxazone | DDC |
CYP3A4 | Midazolam Testosterone Nifedipine |
1‘-Hydroxymidazolam 6β-Hydroxytestosterone Nifedipine-oxide |
Ketoconazole Troleandomycin |
For others, we evaluate the effects of inhibitors on metabolism of a commercially available drug through the establishment of a system for measuring its metabolites and calculating the kinetic parameters using human microsomes and human frozen hepatocytes, etc.