Exploiting serendipity for the discovery of new antimelanoma targets and scaffolds
The 7th of November 2022 17h15
Amphitheater Allais – School of Pharmacy Lille
Abstract : Despite dramatic improvement in the knowledge on resistant forms of melanoma over the last two decades, its treatment is still a challenge. Thus, efficient treatments, especially relying on innovative mode of action, are needed to overcome these resistance phenomena and propose new treatment options to patients in therapeutic failure. We used cellular phenotypic screenings of rationally focused libraries to generate new active hits. Optimization by structure−activity and structure-pharmacological properties relationships provided us lead compounds, that have been used in target identification studies. This led to the validation of an anti-melanoma protein target: GRP78, the master regulator of ER Stress response. Other targets are under investigation like the oncogene MELK. Besides, during hit-to-lead optimizations, several active scaffolds were discovered.