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NB-9402 is an orally bioavailable, brain-penetrant small molecule inhibitor of Sterile Alpha and Toll/Interleukin-1 Receptor Motif-containing protein 1 (SARM1), developed by Nura Bio. SARM1 is a pro-degenerative enzyme that serves as a key executioner of axonal loss across various neurological conditions. Upon activation by axonal stress or injury, SARM1 functions as an NADase, rapidly depleting intracellular nicotinamide adenine dinucleotide (NAD+) levels, which leads to metabolic failure and subsequent axonal fragmentation. By inhibiting SARM1 activity, NB-9402 is designed to preserve axonal structure and function, offering a potential neuroprotective strategy for diseases such as amyotrophic lateral sclerosis (ALS), peripheral neuropathies, and traumatic brain injury. As of late 2023, the compound entered first-in-human Phase 1 clinical testing in Australia to evaluate its safety, tolerability, and pharmacokinetic profile.
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