基于吡啶的 SARM1 小分子抑制剂可缓解 NAD 酶活性引起的细胞死亡。
Pyridine-based small molecule inhibitors of SARM1 alleviate cell death caused by NADase activity.
机构信息
State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.
School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
出版信息
Chem Commun (Camb). 2024 Aug 13;60(66):8724-8727. doi: 10.1039/d4cc02650k.
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.
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 表现出显著的效力，IC50 值达到 0.46 μM。这种卓越的抑制作用显著减少了 SARM1 介导的各种生物模型中的细胞死亡。这一发现通过阻断 SARM1 的激活，为神经退行性疾病提供了有希望的治疗潜力，并推进了我们对这些复杂疾病中分子干预的理解，包括 NAD 代谢的调节。
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