Biochemical and cell-based compound screening

Medicilon offers fully integrated pharmaceutical services for the global scientific community. We focus on providing an exceptional client-centered experience and advancing the drug discovery process.

Email: Marketing@medicilon.com.cn Website: www.medicilon.com

For the development of new tool compounds for chemical biology and medicinal chemistry research, the compound collections synthesized in the Department need to be screened in biochemical and cell-based assays. The objective of the project is to develop such assays in house and with external collaboration partners and to subject the entire compound collection to them.

In order to harness the potential of the synthesized compounds for chemical biology research they are subjected to different biochemical and cell-based compound screening systems.

On the one hand several biochemical assays were set up within the Department. Kinases are among the most important regulating enzymes and they are in the focus of numerous research activities worldwide. Since kinases can up- and downregulate biological phenomena and since the phosphatases are their natural antagonizing partners, phosphatase inhibitors should in principle bear a potential for research similar to kinase inhibitors. However, in contrast to kinase inhibition, the development of potent and selective phosphatase inhibitors, in particular inhibitors of tyrosine and dual specificity phosphatases is a fairly unexplored and developing field.

Based on this reasoning a biochemical screen for inhibition of several tyrosine-, dual specificity- and serine/threonine phosphatases in the 386 well microtiter plate format was set up by Heino Prinz for screening the entire compound collection of the Department. The screen included PTP1B, a target enzyme in the treatment of diabetes type II and the metabolic syndrome, Cdc25A, a phosphatase relevant to cell cycle research and oncology, VHR, a phosphatase that dephosphorylates Map kinases and MptpA and B, two phosphatases secreted by Mycobacterium tuberculosis and putative targets for the development of new anti-tuberculosis drugs.The phosphatase inhibition screens yielded a variety of new inhibitor classes for these enzymes which open up many opportunities for further development.

Cell-based compound screening offers the opportunity to identify both new interesting compounds and new targets for chemical biology and medicinal chemistry research. In addition it unites chemistry and biology in an early stage of research and thereby identifies biologically relevant compounds.More specific screening experiments are expected to be particularly rewarding if cell lines are used that read out the influence of an entire cellular pathway, carrying for instance a known lesion. Therefore, in collaboration with O. Müller we have set up cell-based screens monitoring the Ras and the Wnt-signalling pathway.