DSRM-3716 (5-Iodoisoquinoline) 是一种有效的选择性 SARM1 NADase 抑制剂，IC50 为 75 nM。DSRM-3716 对其他 NAD+ 加工酶、受体和转运蛋白具有选择性。DSRM-3716 具有强大的轴突保护作用。
DSRM-3716 (5-Iodoisoquinoline) is a potent and selective SARM1 NADase inhibitor with an IC50 of 75 nM. DSRM-3716 is selective against other NAD+-processing enzymes, receptors, and transporters. DSRM-3716 provides robust axon protection[1].
DSRM-3716 treatment produces dose-dependent inhibition of cADPR increase (IC50 of 2.8 μM) and substantial preservation of NAD+ in these cultures in a manner consistent with engagement and inhibition of SARM1 enzymatic NADase activity inside the cells[1]. DSRM-3716 prevents neurofilament light chain (NfL) release from severed axons in a dose-dependent manner, with an IC50 of ~2 μM[1]. The potency of DSRM-3716 to inhibit cADPR increase caused by axotomy (IC50 of 2.8 μM) is similar to the potency required to prevent axonal degeneration (IC50 of 2.1 μM)[1]. DSRM-3716 inhibits the SARM1-dependent cell destruction pathway triggered by Rotenone in sensory neurons[1].
[1]. Robert O Hughes, et al. Small Molecule SARM1 Inhibitors Recapitulate the SARM1 -/- Phenotype and Allow Recovery of a Metastable Pool of Axons Fated to Degenerate. Cell Rep. 2021 Jan 5;34(1):108588.
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