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.