Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology

Kingsley Laura J.; He Xiaohui; McNeill Matthew; Nelson John; Nikulin Victor; Ma Zhiwei; Lu Wenshuo; Zhou Vicki W.; Manuia Mari; Kreusch Andreas; Gao Mu-Yun; Witmer Darbi; Vaillancourt Mei-Ting; Lu Min; Greenblatt Sarah; Lee Christian; Vashisht Ajay; Bender Steven; Spraggon Glen; Michellys Pierre-Yves; Jia Yong; Haling Jacob R.; Lelais Gerald

首页> 外文期刊>Journal of Medicinal Chemistry >Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology

【24h】

Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology

机译：基于结构的选择性LONP1抑制剂设计，用于探讨体外生物学

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

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.

机译：LONP1是一种AAA+蛋白酶，通过去除受损或错误折叠的蛋白质来维持线粒体内稳态。LONP1活性和表达的增加促进癌细胞增殖和对凋亡诱导试剂的抵抗。尽管LONP1在人类生物学和疾病中具有重要意义，但文献中很少描述LONP1抑制剂。在此，我们报告了利用基于结构的药物设计开发选择性硼酸基LONP1抑制剂，以及与各种抑制剂结合的人类LONP1的第一个结构。我们的努力导致了几种纳摩尔LONP1抑制剂，它们对20S蛋白酶体几乎没有活性，可以作为研究LONP1生物学的工具化合物。

著录项

来源
《Journal of Medicinal Chemistry》 |2021年第8期|共13页
作者
Kingsley Laura J.; He Xiaohui; McNeill Matthew; Nelson John; Nikulin Victor; Ma Zhiwei; Lu Wenshuo; Zhou Vicki W.; Manuia Mari; Kreusch Andreas; Gao Mu-Yun; Witmer Darbi; Vaillancourt Mei-Ting; Lu Min; Greenblatt Sarah; Lee Christian; Vashisht Ajay; Bender Steven; Spraggon Glen; Michellys Pierre-Yves; Jia Yong; Haling Jacob R.; Lelais Gerald;
展开▼
作者单位

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

Novartis Res Fdn Genom Inst San Diego CA 92121 USA;

展开▼
收录信息
原文格式 PDF
正文语种 eng
中图分类药学;
关键词

相似文献

外文文献
中文文献
专利

1. Algorithmic challenges in structure-based drug design and NMR structural biology [J] . Lincong WANG, Shuxue ZOU, Yao WANG 中国电气与电子工程前沿：英文版 . 2012,第001期
2. Structure-based design, synthesis of novel probes for cytochrome P450 OleT [J] . Dumei Ma, Libo Zhang, Yingwu Yin, 中国化学快报（英文版） . 2021,第004期
3. Structure-based drug design of a novel family of chalcones as PPARα agonists: virtual screening, synthesis, and biological activities in vitro [J] . Xiang-hua LI, Han-jun ZOU, An-hui WU, 中国药理学报：英文版 . 2007,第012期
4. Exploiting differences in caspase-2 and -3 S subsites for selectivity: structure-based design, solid-phase synthesis and in vitro activity of novel substrate-based caspase-2 inhibitors. [J] . Maillard MC, Brookfield FA, Courtney SM, Bioorganic and medicinal chemistry . 2011,第19期

机译：利用caspase-2和-3 S亚位点的差异进行选择性：基于结构的设计，固相合成和新型基于底物的caspase-2抑制剂的体外活性。
5. Exploiting differences in caspase-2 and -3 S subsites for selectivity: structure-based design, solid-phase synthesis and in vitro activity of novel substrate-based caspase-2 inhibitors. [J] . Maillard MC, Brookfield FA, Courtney SM, Bioorganic and medicinal chemistry . 2011,第19期

机译：利用caspase-2和-3 S亚位点的差异进行选择性：基于结构的设计，固相合成和新型基于底物的caspase-2抑制剂的体外活性。
6. Structure-Based Design of Selective beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitors: Targeting the Flap to Gain Selectivity over BACE2 [J] . Fujimoto Kazuki, Matsuoka Eriko, Asada Naoya, Journal of Medicinal Chemistry . 2019,第10期

机译：基于结构的选择性β-位点淀粉样蛋白前体蛋白质切割酶1（BACE1）抑制剂：靶向翼片以获得对BACE2的选择性
7. Chapter 9 A Structure-Based Design Approach to Plant Selective 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors [C] . Debra L. Camper, Marshall H. Parker Synthesis and chemistry of agrochemicals VII . 2007

机译：第9章基于结构的植物选择性4-羟基苯丙酮酸双加氧酶抑制剂的设计方法
8. Structure-based design and synthesis of selective small molecule inhibitors for Mcl-1, an important cancer target [D] . McNulty, Oren 2015

机译：Mcl-1（一种重要的癌症靶标）的选择性小分子抑制剂的基于结构的设计和合成
9. Unique Ligand Binding Sites on CXCR4 Probed by a Chemical Biology Approach: Implications for the Design of Selective Human Immunodeficiency Virus Type 1 Inhibitors [O] . Won-Tak Choi, Shaomin Tian, Chang-Zhi Dong, 2005

机译：化学生物学方法探测CXCR4上的独特配体结合位点：对选择性人类免疫缺陷病毒1型抑制剂设计的意义。
10. Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology [O] . -1

机译：基于结构的选择性LonP1抑制剂设计，用于探测体外生物学
11. Structure-Based Design of erbB-2 Selective Small Molecule Kinase Inhibitors [R] . Wang, S. 2005

机译：基于结构的erbB-2选择性小分子激酶抑制剂的设计

Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology

摘要

著录项

相似文献

相关主题

期刊订阅