CYP Inhibition

The inhibition of CYP isoenzymes is one of the key aspects in drug-drug interaction.

Drug Discovery Screen

The percentage inhibition of different CYP marker reaction activites by the test item is determined.

Quantity of test item required: 1 mg (pre-weighted)
Turnaround time of draft report: 15 working days

Study Design

• multiple CYP isoforms (mircosomes or human recombinant enzymes)
• triplicates
• one concentration of CYP
• 50 µM of test item
• 30 min
• neagtive controls: CYP marker reactions:

1A1/2 (7-ethoxyresorufin O-deethylation)
2A6 (coumarin 7-hydroxylation)
2B6 (S-mephenyoin N-demethylation)
2C8 (paclitaxel 6-hydroxylation)
2C9 (diclofenac 4'-hydroxylation)
2C19 (S-mephenytoin 4'-hydroxylation)
2D6 (bufuralol hydroxylation)
2E1 (chloroxazone 6a-hydroxylation)
3A4/5 (testosterone 6b-hydroxylation)
4A11 (lauric acid-hydroxylation)
11B1 (11-deoxycortisol 11b-hydroxylation)
11B2 (deoxycorticosterone-hydroxylation)

• positive controls: CYP reference inhibitors:

1A1/2 (furafylline)
2A6 (8-methoxypsoralene)
2B6 (triethylenethiophosphoramide)
2C8 (ketoconazole)
2C9 (sulfaphenazole)
2C19 (omeprazole)
2D6 (quinidine)
2E1 (diethyldithiocarbamate)
3A4/5 (ketoconazole)
4A11 (10-(imidazolyl)-decanoic acid)
11B1 (metyrapone)
11B2 (ketoconazole)

Analytics

• detection of metabolite formed in the marker reaction