Cerep offers a range of over 175 assays (including 22 new assays)
for rapid evaluation of the pharmaceutical properties and safety of drug discovery compounds:
Cerep has developed methods for the accurate and rapid assessment of the solubility, lipophilicity, ionization constant, chemical
stability, protein binding and blood partitioning characteristics of chemical compounds.
In vitro drug absorption/ drug transport
Cerep has developed an efficient test to assess the intestinal permeability of compounds in both the absorptive and the secretory directions.
The TC7 sub-clone of the Caco-2 cell line originally derived from the human intestine is used in this in vitro absorption model. Also available
are Madin-Darby canine kidney cells (MDCKII) and MDCKII cells expressing the human MDRI gene (MDRI-MDCKII). Data obtained from the permeability
tests can be used to:
Predict drug absorption in human
Identify potential substrates and/or inhibitors of efflux systems such as P-glycoprotein
In vitro drug metabolism
There is a significant advantage to obtaining metabolism data as early as possible in the drug discovery process. Hepatic metabolism is a primary
determinant of pharmacokinetic behavior, and rapid first-pass metabolism is a major cause of low bioavailability. At Cerep, a variety of assay
matrices including pooled liver microsomes, pooled liver S9 fraction, hepatocytes, human recombinant cytochrome P450s, UGTs, blood, and plasma
are used for the metabolic assessment of hits, leads, and new pharmaceutical compounds. The results of the metabolism studies are useful in:
Determining the initial rate at which compounds are metabolized
Investigating the major pathways of drug metabolism
Identifying probable metabolites
Predicting in vivo pharmacokinetic properties
Investigating the potential for drug-drug interactions
In vivo PK/BBB - Bioanalytical support
Obtaining early stage pharmacokinetic data in the evaluation of new chemical entities is a prerequisite for successful animal pharmacology and
toxicology studies. Cerep has developed pharmacokinetic assays in rats and mice. In addition, Cerep has also developed in vivo blood-brain barrier
assays in rats and mice to evaluate the brain penetration of compounds.
Cerep has developed three distinct assays – recovery, linearity, quantitative bioanalysis – to support in vivo pharmacokinetic studies. These assays
are designed to ensure that reliable and useful data are ultimately obtained. In each case state-of-the-art HPLC-MS/MS instrumentation and optimized
analytical methods allow for detection of picogram quantities of analyte in a biological matrix.
It is not uncommon that a patient may be taking several drugs, simultaneously, for the treatment of one or more health related issues. A drug may
affect or be affected by other co-administered drugs. Metabolism-based drug-drug interactions occur when a drug inhibits or induces the activity
of a drug metabolizing enzyme, which catalyzes the metabolism of a concomitant drug. Metabolism-based drug-drug interactions (DDI) are one of the
major factors that cause drug failures during drug development. Early stage screening of compounds for potential drug-drug interactions using in
vitro techniques becomes necessary in order to decrease late stage compound attrition.
Cerep offers a range of assays to determine the metabolism of compounds and their potential for drug-drug interactions.
High-throughput cocktail CYP inhibition
CYP inhibition- recombinant CYPs or liver microsomes
Time-dependent CYP inhibition
In order to be able to assess the potential toxicity of compounds as early as possible, Cerep has developed a set of in vitro tests which address:
In vitro toxicity
Many assays are suitable for evaluating the ADME-Tox properties of compounds early in the drug discovery process while others are designed
with the intent to meet regulatory requirements making them suitable for later stage development.