Max Lewandowski

 

Research Interest

The increasing incidence of neurodegenerative diseases such as Alzheimer's disease (AD), multiple sclerosis (MS) or Parkinson's disease (PD) will pose major challenges to our aging society. Since basic pathomechanisms remain elusive,  major focus is on the validation of new targets.

In this context, the group of ligand-sensitive nuclear receptors turned out to be promising. Notably, the family of retinoid X receptors (RXR), among other beneficial effects, have shown great potential in the therapy of mentioned diseases. Unfortunately, traditional RXR ligands suffer from both poor physicochemical properties and subtype selectivity.

In regard to this challenge, my research is based on the in silico conceptualization, generation and in vitro testing of advanced tool compounds for the RXR - superfamily. In detail I focus on the synthesis of modern molecular tools, based on so-called "Beyond-rule-of-5" compounds such as e.g. PROTACS. Furthermore, I develop a new “Affinity selection LC-MS/MS” Assay, to validate lead compound by orthogonal testing.

Publications

Sai, M.; Hank, E. C.; Lewandowski, M.; Kasch, T.; Marschner, J. A.; Merk, D. Development of Potent and Selective Nurr1 Agonists from Amodiaquine By Scaffold Hopping and Fragment Growing. Commun. Chem., 2024, 7, 149. DOI

Lewandowski, M.; Carmina, M.; Knümann, L.; Sai, M.; Willems, S.; Kasch, T.; Pollinger, J.; Knapp, S.; Marschner, J. A.; Chaikuad, A.; Merk, D. Structure-Guided Design of a Highly Potent Partial RXR Agonist with Superior Physicochemical Properties. J. Med. Chem., 2024, 67, 2152–2164. DOI