Laura J. Kingsley*, Xiaohui He, Matthew McNeill, John Nelson, Victor Nikulin, Zhiwei Ma, Wenshuo Lu, Vicki W. Zhou, Mari Manuia, Andreas Kreusch, Mu-Yun Gao, Darbi Witmer, Mei-Ting Vaillancourt, Min Lu, Sarah Greenblatt, Christian Lee, Ajay Vashisht, Steven Bender, Glen Spraggon, Pierre-Yves Michellys, Yong Jia, Jacob R. Haling, Gérald Lelais*
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引用次数: 4
Abstract
LONP1 is an AAA+ protease that maintains mitochondrial homeostasis by removing damaged or misfolded proteins. Elevated activity and expression of LONP1 promotes cancer cell proliferation and resistance to apoptosis-inducing reagents. Despite the importance of LONP1 in human biology and disease, very few LONP1 inhibitors have been described in the literature. Herein, we report the development of selective boronic acid-based LONP1 inhibitors using structure-based drug design as well as the first structures of human LONP1 bound to various inhibitors. Our efforts led to several nanomolar LONP1 inhibitors with little to no activity against the 20S proteasome that serve as tool compounds to investigate LONP1 biology.
期刊介绍：
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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