Project Details
Projekt
Target basierte Entwicklung neuer Hemmstoffe der Lysin-Dementhylase LSDI und deren Einfluss auf die Regulation des Androgenrezeptors
Subject Area
Pharmacy
Term
from 2009 to 2012
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 93713832
Histone modifying enzymes are key players of the epigenetic regulation in eukaryotic cells. The lysine specific demethylase 1 (LSD1) demethylates histone proteins and is a higly promising target for combatting prostate cancer. Disovery and development of new LSD1 inhibitors are still rather limited. In this project we have developed new potent LSD1 inhibitors with cellular activity through a combination of virtual screening, biological testing and medicinal chemistry. A highlight is the reversible LSD1 inhibitor namoline that blocks prostate cancer growth in vivo. In this proposal we want to provided new selective LSD1 inhibitors with improved anticancer activity in vitro and in vivo. We will combine lead structure guided medicinal chemistry, structure based molecular modelling and advanced preclinical models. New inhibitors will be tested in cells for their effects on androgen dependent transcription and growth. Inhibitors with high cellular activity are candidates for animal testing in genetically modified animals and in vivo-tumor models. The impact of the inhibitors on histone modifications on a genome wide scale is an important part of this project. This investigations will lead to an improved understanding of the biological role of LSD1 and its therapeutic potential and provide potential drug candidates for cancer therapy.
DFG Programme
Research Grants
