Development of Compounds Targeting Resistant Cancer – Experiences with Plexus Connect in an Academic Setting
Our research interests focus on compounds that have the potential to overcome multidrug resistance in cancer. Compounds showing paradoxical toxicity against otherwise multidrug resistant cells were first identified in a publicly available database comprising the in vitro toxicity profiles of >40.000 compounds on 60 cancer cell lines (DTP database, NCI). Our aim was to increase the potency of the initial hits by exploring the chemical space around scaffolds identified in the in silico screen.
Commercially available compounds of interest were identified in a vendor database using substructure and similarity searches in Instant JChem (IJC). Non-available and innovative molecules were synthesized. Screening data of biological activity was analyzed by a custom software; IC50 values were imported into IJC to merge biological and chemical data. Structure activity relationships were investigated combining different techniques and tools ranging from “paper-chemistry” to JChem for Excel and the application of Plexus Connect for multivariate analysis. Further IJC functions, especially of JChem for Excel are used for the analysis and visualization of Structure-Activity-Relationships within the datasets.