After a successful HTS campaign, the huge amount of data is analysed by COMAS Cheminformatics and MedChem scientists. Using a range of cheminformatics and visualization tools the most promising scaffolds will be identified. Validated hits may enter a chemical optimization program to enhance potency or cellular penetration. If available, protein structural data can be used to guide new compound design.
Even low-potency hit compounds which may originate from cell-based screens can be improved by iterative cycles of hit optimization guided by our experienced MedChem team.
Promising scaffolds with optimization potential that were identified in the analysis of the HTS campaign may enter a chemical optimization program in the COMAS synthesis lab. In case it is desirable, a novel synthesis route is developed and new derivatives will be designed and synthesized over multiple synthesis steps, with the typical targeted amount of a test compound being between 10 and 100 mg. All state-of-the-art chemical reactions can be performed, including hydrogenation, organometallic reactions and microwave synthesis. Compounds are routinely analysed by LCMS and NMR (1H, 13C) and the reactions are documented in an electronic labjournal. Where necessary, resources at the nearby Max-Planck institute or the university (TU Dortmund) can be used