MK-8153

An anal. of 156 published/clin. candidates from the Journal of Medicinal Chem. between 2018 and 2021 was conducted to identify lead generation strategies most frequently employed leading to drug candidates.As in a previous publication, the most frequent lead generation strategies resulting in clin. candidates were from known compounds (59%) followed by random screening approaches (21%).The remainder of the approaches included directed screening, fragment screening, DNA-encoded library screening (DEL), and virtual screening.An anal. of similarity was also conducted based on Tanimoto-MCS and revealed most clin. candidates were distant from their original hits; however, most shared a key pharmacophore that translated from hit-to-clin. candidate.An examination of frequency of oxygen, nitrogen, fluorine, chlorine, and sulfur incorporation in clin. candidates was also conducted.The three most similar and least similar hit-to-clin. pairs from random screening were examined to provide perspective on changes that occur that lead to successful clin. candidates.