Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology
| العنوان: | Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology |
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| المؤلفون: | Mari Manuia, Wenshuo Lu, Laura J. Kingsley, Zhiwei Ma, Vicki Zhou, Darbi Witmer, Glen Spraggon, Mu-Yun Gao, Pierre-Yves Michellys, Min Lu, Yong Jia, Matthew McNeill, Sarah Greenblatt, Bender Steven Lee, Andreas Kreusch, Gerald Lelais, Xiaohui He, Victor Nikulin, Mei-Ting Vaillancourt, Christian C. Lee, Jacob R. Haling, John Nelson, Ajay A. Vashisht |
| المصدر: | Journal of Medicinal Chemistry. 64:4857-4869 |
| بيانات النشر: | American Chemical Society (ACS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Drug, 0303 health sciences, Protease, Cancer cell proliferation, media_common.quotation_subject, medicine.medical_treatment, 01 natural sciences, 20s proteasome, In vitro, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, 03 medical and health sciences, chemistry.chemical_compound, chemistry, Biochemistry, Drug Discovery, medicine, Molecular Medicine, Structure based, Protein folding, Boronic acid, 030304 developmental biology, media_common |
| الوصف: | 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. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::b50a3181ddf89b7c66263433d103701a https://doi.org/10.1021/acs.jmedchem.0c02152 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........b50a3181ddf89b7c66263433d103701a |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204804 00222623 |
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