Current advances in the structure-activity relationship (SAR) analysis of the old/new 18-kDa translocator protein ligands.

IF 3.9 2区化学 Q2 CHEMISTRY, APPLIED Molecular Diversity Pub Date : 2024-12-04 DOI:10.1007/s11030-024-10963-0

Priya Singh, Vijay Kumar Singh, Chandraprakash Gond, Deepika Singh, Anjani Kumar Tiwari

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Abstract

The translocator protein 18 kDa (TSPO) is a crucial external mitochondrial protein involved in cholesterol translocation, which is essential for steroid production. As a primary marker of neuroinflammation, TSPO has been implicated in the development and progression of various neurodegenerative and neuropsychiatric disorders. This review highlights the structural diversity of TSPO ligands, many of which have undergone modifications from selective central benzodiazepine receptor (CBR) ligands to enhance their affinity for TSPO. The paper discusses the significant advancements in the design of these ligands, emphasizing their binding efficacy and specificity. Additionally, it provides an update on the progress of several TSPO ligands that have advanced to clinical trials. The review aims to elucidate the structure-activity relationships (SAR) that govern the interaction between TSPO and its ligands, thereby offering insights into the development of new therapeutic agents targeting TSPO for the treatment of neuroinflammatory conditions. Overall, this work provided an update on previous finding and serves as a valuable resource for researchers in the field.

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新旧18kda转运蛋白配体的构效关系（SAR）分析进展。

转运蛋白18kda （TSPO）是一种重要的线粒体外蛋白，参与胆固醇转运，这对类固醇的产生至关重要。作为神经炎症的主要标志物，TSPO与各种神经退行性疾病和神经精神疾病的发生和进展有关。本文综述了TSPO配体的结构多样性，其中许多配体经过选择性中枢苯二氮卓受体（CBR）配体的修饰，以增强其对TSPO的亲和力。本文讨论了这些配体设计的重大进展，强调了它们的结合功效和特异性。此外，它还提供了几个已进入临床试验的TSPO配体的最新进展。本文旨在阐明控制TSPO与其配体之间相互作用的结构-活性关系（SAR），从而为开发针对TSPO治疗神经炎症疾病的新药物提供见解。总的来说，这项工作为以前的发现提供了更新，并为该领域的研究人员提供了宝贵的资源。

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来源期刊

Molecular Diversity 化学-化学综合

CiteScore

7.30

自引率

7.90%

发文量

219

审稿时长

2.7 months

期刊介绍： Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;