The core objective of this project area is to identify and optimize small molecules that modulate aging and senescence- associated molecular mechanisms. We can build here on previous results from our consortium partners, who have already investigated several promising small molecules in their labs. Our aim is to further optimize these compounds in terms of potency and pharmacokinetic properties.

Besides small molecules, our collaboration partners within the consortium have also investigated pharmacological targets in great detail, which play a central role in several ageing-related signaling cascades. However, only a few, and in some cases none at all, confirmed ligands are currently available for these targets. We will apply our extensive computational drug discovery expertise to identify novel molecules that interact with these targets of interest and modulate their function in a beneficial manner. This requires that we combine the different molecular modelling, virtual screening, and data analysis methods available in our lab.

Furthermore, and in close collaboration with Prof. Sabrina Büttner in Stockholm (https://buttner-lab.com/), we will conduct an unbiased medium-throughput compound screen in yeast to identify entirely novel chemical matter.

Therefore, we will apply multiple complementary and independent hit identification strategies in this project, which will allow us to maximize our chances of successfully identifying promising bioactive molecules. All interesting compounds will then be further optimized using an iterative design cycle. For this purpose, we will work in close collaboration with our wet lab colleagues and combine computational drug design and experimental techniques.