Diploma Worker, AstraZeneca Gothenburg, 30 hp

Title:

An automatied high troughput screening assay for metabolic stability in 384 well format.

Aug 28, 2017 - Jan 14, 2018

Project description:

Introduction:

It is very important to characterize new chemical entities in very early phase of drug discovery process. The characterization is done by high throughput screening to determine physical-chemical properties e.g. logD, solubility, protein binding and metabolic stability.

Background

Metabolic stability is a measure of a compound’s susceptibility to biotransformation. Depending on what system is used, metabolic stability studies can give information on the qualitative or quantitative roles of organs, enzymes, and metabolic routes in the disposition of test compounds.

In the pharmaceutical industry, metabolic stability studies are routinely done with hepatocytes or microsomal fractions. The results from metabolic stability study are usually reported as Clint (clearance) and a t1/2 (half –life) and are used for selecting and designing drugs with favorable pharmacokinetic properties and for the predictions of drugs bioavaibility in humans hence the drugs cannot be administrated to humans in this early phase.

The invitro systems for study of metabolic stability are very well established in pharmaceutical industry since 20 years ago. The challenge for this project is to scale down assay´s incubations volumes for 384 plate format, optimize incubations parameters e.g. temperature and oxygen supply during incubation time. Establish robotic pipetting of cell suspension into the incubation plate. Validate the new protocols to ensure quality of the assay which will be crucial if the assay could be successfully taken into production. Such an approach will reduce compound’s amount needed for the assay and reduce cells consumption.

Project

The student will be working with the Hamilton automated platform to conduct incubations both in hepatocytes and liver microsmes. Perform analysis using UPLC-MSMS conditions to determine depletion of the parent compound and evaluate results with help of Gendata Screener. In collaboration with CM establish assay ready plates with appropriate volume of the test solution in 384 plate form.

Last date to submit your application is April 15th.

For questions please contact Fredrik Wågberg at AstraZeneca. E-mail: fredrik.wagberg@astrazeneca.com