SN 2

SN 2 is a potent activator of TRPML3 ion channel with an EC₅₀ of 1.8 μM^[1]. SN 2 also acts as a potent inhibitor of Dengue virus 2 (DENV2) and Zika virus (ZIKV)^[2]. IC50 & Target: EC50: 1.8±0.13 μM (TRPML3), >29.9 μM (TRPML1)^[1] In Vitro: The conductance of TRPML3 channels is estimate, when activated with 10 μM SN-2 is approximately 10 pS at ?80 mV. TRPML3-expressing HEK293 cells are perfused with a series starting with compound alone (in SBS), with compound in ELS, and finally with ELS alone. Two representative compounds, SF-24 and SN-2, are tested. SF-24 is one of the least effective compounds, and SN-2 is one of the most active ones. SN-2 has a similar synergistic effect, also reaching up-to 10-fold enhancement of the combined response when compared with the individual responses, reaching average current densities of up to 3 nA/pF at ?80 mV. Dominant negative TRPML3(D458K) is highly effective in eliminating SN-2-induced activity in epidermal melanocytes, suggesting that SN-2 activates a channel that is not responsive in presence of TRPML3(D458K). Such a dominant negative action might be attributed to potential heteromerization of TRPML3(D458K) with an SN-2-responsive channel^[1].