DSRM-3716

DSRM-3716 (5-iodoisoquinoline) is a potent and selective small molecule inhibitor of the **Sterile Alpha and TIR Motif Containing 1 (SARM1)** NAD+ hydrolase (NADase), with an IC50 of 75 nM. SARM1 is a key executioner of axonal degeneration; upon activation by injury or metabolic stress, it rapidly depletes cellular nicotinamide adenine dinucleotide (NAD+), leading to axonal fragmentation. DSRM-3716 works by inhibiting this NADase activity, thereby maintaining NAD+ levels and preventing the accumulation of cyclic adenosine diphosphate ribose (cADPR). Preclinical studies have demonstrated that DSRM-3716 protects mouse dorsal root ganglia (DRG) neurons and human iPSC-derived motor neurons from degeneration induced by axotomy or mitochondrial dysfunction. Additionally, research suggests that SARM1 inhibition may have therapeutic potential in chronic inflammatory conditions such as rheumatoid arthritis by preventing pro-inflammatory macrophage death.

Other names

5-iodoisoquinoline