SARM1-IN-7 is a potent, orally active inhibitor of SARM1, targeting its active site (orthosteric). This compound persistently enhances SARM1's enzymatic activity, leading to exacerbated NAD depletion at suboptimal concentrations. In both cell and mouse models with activated SARM1, SARM1-IN-7 exhibits dual effects: high doses provide cell/neuron protection, whereas low doses intensify cell/neuron damage. SARM1-IN-7 is applicable in studies of axonal degeneration.