Issue 66, 2024

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

Abstract

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.

Graphical abstract: Pyridine-based small molecule inhibitors of SARM1 alleviate cell death caused by NADase activity

Supplementary files

Article information

Article type
Communication
Submitted
02 Jan 2024
Accepted
18 Upu 2024
First published
18 Upu 2024

Chem. Commun., 2024,60, 8724-8727

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

Q. Tang and H. Yin, Chem. Commun., 2024, 60, 8724 DOI: 10.1039/D4CC02650K

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