Structure-based modification of pyrazolone derivatives to inhibit mTORC1 by targeting the leucyl-tRNA synthetase-RagD interaction

In this study, in silico physicochemical properties and metabolite analysis of BC-LI-0186 are used to investigate the addition of functional groups to improve solubility and microsomal stability. In vitro experiments demonstrated that 7b and 8a had improved chemical properties while still maintaining inhibitory activity against mTORC1. The results suggest a new strategy for the discovery of novel drug candidates and the treatment of diverse mTORC1-related diseases.PMID:33979735 | DOI:10.1016/j.bioorg.2021.104907

Source: Bioorganic Chemistry - May 12, 2021 Category: Chemistry Authors: Jae Hyun Kim Kilsoo Jung Chulho Lee Doona Song Kibum Kim Hee Chan Yoo Seung Joon Park Jong Soon Kang Kyeong-Ryoon Lee Sunghoon Kim Jung Min Han Gyoonhee Han Source Type: research