Small-molecule Mediated Modulation of Signaling Pathways
The talk will focus on small molecule–mediated modulation of signaling pathways. Systematic application of small molecule modulators of protein function for the study of biological networks involved in signaling pathways lies at the heart of an experimental approach termed as Chemical Biology.
Wnt signaling is a branch of a functional network involved in a broad range of biological processes, such as development and homeostasis. It is one of the fundamental oncogenic pathways, and is implicated in multiple cancers. Thus targeting this pathway is an attractive therapeutic approach. Within the framework of biology oriented synthesis (BIOS), screening of the natural product inspired withanolide-based compound collection revealed potent inhibitors of Wnt signaling (IC50 = 100 nM) in human colorectal cancer cells. An assortment of different biochemical, cell biological and proteomic methods-based primary and secondary assays, were used to validate the bioactivity of our „lead compound“ in the Wnt pathway. Our efforts towards identification of the compound’s target protein will be discussed. Through a similar approach in a parallel project, a potent and selective small molecule inhibitor of cytokinesis was identified and validated.