Fragment-to-Lead Medicinal Chemistry Publications in 2022

Abstract

This Perspective is the eighth in an annual series that summarizes successful fragment-to-lead (F2L) case studies published each year. A tabulated summary of relevant articles published in 2022 is provided, and features such as target class, screening methods, and ligand efficiency are discussed both for the 2022 examples and for the combined examples over the years 2015−2022. In addition, trends and new developments in the field are summarized. In 2022, 18 publications described successful fragment-to-lead studies, including the development of three clinical compounds (MTRX1719, MK-8189, and BI-823911). ■ SIGNIFICANCEFragment-based methodologies have become firmly established within the drug discovery community, and with the recent FDA approval of capivasertib, there are now seven fragment-derived drugs approved for clinical use. This Perspective provides case studies of successful fragment-tolead examples for 2022 and discusses various trends, including target classes, screening methods, and physicochemical properties, compared with previous years.

NIMO: A Natural Product-Inspired Molecular Generative Model Based on Conditional Transformer

“…NIMO showed excellent enrichment ability in the above specific activity-oriented task. Next, we spotlighted the fragment-derived methods and strategies for the effectiveness of virtual library development [45,46]. We proposed a general approach to design antibacterial discovery libraries.…”