Expanding the repertoire of tumor microenvironment radiotracers through cheminformatic analysis

Abstract Drug development using cheminformatic methods has been employed frequently with many successful cases, allowing that computer assisted drug design accelerate scientific progress. Considering all the cheminformatic advances, here in we analyze the potential of these methods in nuclear medicine, specifically for the proposal of new radiotracers. To illustrate the method, the fibroblast activation protein was used as a molecular target and three databases containing compounds with affinity towards this target were constructed. Different cheminformatic methods (exploratory data analysis, activity cliffs plots, dimensionality reduction) were implemented to find different structural patterns which could be considered as starting point for the design of new radiotracers, considering factors such as main physicochemical characteristics, activity-cliffs, scaffold frequencies, among others.