基于吡啶的 SARM1 小分子抑制剂可减轻 NAD 酶活性导致的细胞死亡。

IF 4.3 2区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Chemical Communications Pub Date : 2024-08-13 DOI:10.1039/d4cc02650k

Qingxuan Tang , Hang Yin

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引用次数: 0

摘要

我们的研究揭示了一系列基于吡啶的 SARM1 抑制剂，其中先导化合物 TH-408 具有显著的效力，其 IC50 值为 0.46 μM。在不同的生物模型中，这种特殊的抑制作用大大减少了 SARM1 介导的细胞死亡。这一发现凸显了通过破坏 SARM1 的活化来治疗神经退行性疾病的巨大潜力，并推进了我们对这些复杂疾病的分子干预（包括 NAD+ 代谢调控）的了解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Pyridine-based small molecule inhibitors of SARM1 alleviate cell death caused by NADase activity†

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Pyridine-based small molecule inhibitors of SARM1 alleviate cell death caused by NADase activity†

Our investigation has unveiled a series of pyridine-based SARM1 inhibitors, with the lead compound TH-408 exhibiting remarkable potency, achieving an IC50 value of 0.46 μM. This exceptional inhibitory effect significantly curtailed SARM1-mediated cell death across diverse biological models. This finding highlights the promising therapeutic potential for neurodegenerative disorders by disrupting SARM1 activation and advances our understanding of molecular interventions in these complex disorders, including the regulation of NAD⁺ metabolism.

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来源期刊

Chemical Communications 化学-化学综合

CiteScore

8.60

自引率

4.10%

发文量

2705

审稿时长

1.4 months

期刊介绍： ChemComm (Chemical Communications) is renowned as the fastest publisher of articles providing information on new avenues of research, drawn from all the world''s major areas of chemical research.