(S)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1H-benzimidazol-2-amine

(S)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1H-benzimidazol-2-amine, commonly referred to as compound 1 (S), is a small molecule inhibitor of small conductance calcium-activated potassium (SK) channels, with selectivity for the SK2 (KCNN2) and SK3 (KCNN3) subtypes. It is the (S)-enantiomer of the benzimidazole derivative whose (R)-enantiomer is the potent SK channel inhibitor NS8593. Compound 1 (S) functions as a negative allosteric modulator by decreasing the calcium sensitivity of the channel's gating mechanism, thereby inhibiting the potassium current. In the context of oncology research, particularly pancreatic ductal adenocarcinoma (PDAC), compound 1 (S) has been used to elucidate the role of SK2 channels in mediating communication between cancer-associated fibroblasts (CAFs) and tumor cells. This signaling axis, which involves SK2-regulated calcium dynamics and the secretion of growth factors like EGF, is a critical driver of tumor progression and metastasis. The compound was originally identified and synthesized by NeuroSearch A/S.