ArticleBiomedicines2024
Characterization of Novel SARM1 Inhibitors for the Treatment of Chemotherapy-Induced Peripheral Neuropathy.
Article in Biomedicines, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Preclinical Pharmacokinetic and Pharmacological Profiling of B339, a Novel SARM1 Inhibitor for the Treatment of Vincristine-induced Peripheral Neuropathy.Pharmaceutical research · 2026Article
- Article
- Enhancing peripheral nerve regeneration in aging: the role of Schwann cells, c-Jun, and emerging therapeutic strategies.GeroScience · 2026Review
- The rise and fall of SARM1 base-exchange inhibitors.Communications chemistry · 2026Article
- New mechanistic insight into SARM1 activation: TRIM32-mediated ubiquitination is a key lever that actuates SARM1's catalytic action, leading to axon degeneration and cell death.Frontiers in neural circuits · 2026Article
- Addressing the Needs of Breast Cancer Survivors.Current oncology reports · 2025Review
- The role of NADnpj metabolic health and disease · 2025Review
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSterile α and Toll/IL-1 receptor motif-containing 1 (SARM1) is a central regulator of programmed axon death and a crucial nicotinamide adenine dinucleotide (NAD+) hydrolase (NADase) in mammalian tissues, hydrolyzing NAD+ and playing an important role in cellular NAD+ recycling. Abnormal SARM1 expression is linked to axon degeneration, which causes disability and disease progression in many neurodegenerative disorders of the peripheral and central nervous systems.
methodsIn this study, we use PC6 assay of hydrolase activity, DRG axon regeneration and CIPN model to screen for potent SARM1 Inhibitors.
resultsTwo novel SARM1 inhibitors (compound 174 and 331P1) are charcterized for its high potency for SARM1 NADase. In a chemotherapy-induced peripheral neuropathy (CIPN) myopathy model, compound 331P1 treatment prevented the decline in neurofilament light chain (NfL) levels caused by axonal injury in a dose-dependent manner, associated with elevated intraepidermal nerve fiber (IENF) intensity in mouse foot paw tissue, suggesting its functionality in reversing axon degeneration.
conclusionsThe newly designed SARM1 inhibitor 331P1 is a promising candidate due to its excellent in vivo efficacy, favorable CYP inhibition properties, and attractive safety profiles. The 331P1 compound possesses the potential to be developed as a novel neuroprotective therapy that can prevent or halt the neurodegenerative process in CIPN.
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