Pan-Assay INterference Substances (PAINS) is a concept that have dominated the small molecule drug discovery research since 2010. We cannot pass over the importance of PAINS as it saves time and money especially in its original scope: Compound selections for high-throughput screening. However, some scaffolds have been indicted as PAINS without sufficient evidences except including some link to certain PAINS flagged substructures. We have had extensive interest in 3,5-dihydro-4H-imidazol-4-one (imidazolone) as a scaffold for designing newer therapies, especially against malignant diseases. However, we found that imidazolone have been flagged in literature as one of PAINS worst offenders. Indeed, there are reasons for researchers to think of imidazolones as PAINS since they contain electrophilic Michael acceptor moiety and extended conjugation that makes them colored and/or fluorescent. Consequently, it was concluded by leading literature that all imidazolone derivatives should be excluded from drug discovery research. Worse, most of the imidazolone studies appear in low-quality research publications.<br/>In this presentation, we will evaluate issues pertinent to one of our discovered leads, KIM-161 (Structure below) because it features an imidazolone domain that was found important for its cytotoxic activities against cancer cell lines. Instead of giving up the compound due to its adherence to imidazolones, we interrogated its druggability by a battery of chemical and biological investigations. We wish that you come to our poster and ask hard questions why we are going against the stream of PAINS characterization when we discuss KIM-161 and imidazolones in general.

Re-assessing the druggability vs. PAINS characters of 3,5-dihydro-4H-imidazol-4-one: The case of KIM-161

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.