TRPM7 (transient receptor potential cation channel, subfamily M, member 7) consists of two distinct functional moieties: an ion channel segment and a protein kinase domain. TRPM7 was found to be a ubiquitously expressed Mg²⁺-sensitive channel highly permeable to a broad range of divalent cations. TRPM7 regulates many essential cellular functions such as cellular Mg²⁺ homeostasis, cell spreading and mechanosensitivity. Recently we have shown that the negative modulator of SK1-3 channels, N-[(1R)-1,2,3,4-Tetrahydro-1-naphthalenyl]-1H-Benzimidazol-2-amine (NS8593), is also a potent inhibitor of TRPM7 currents. The goal of this work is to elucidate mechanisms of NS8593 action on TRPM7. Using the patch-clam technique we examined the concentration-dependent suppression of TRPM7 activity by NS8593 in the absence or presence of internal Mg²⁺ (300 mM) and observed a 3.7-fold rightward shift of the IC₅₀ value (1.6 and 5.9 mM, respectively), suggesting that NS8593 may interfere with Mg²⁺-dependent gating of the channel. In line with this notion we observed that a point mutation in the pore-forming loop of TRPM7 (Y1049P) increased apparent affinity of the channel to NS8593. In contrast, two kinase deficient mutants, TRPM7-K1646R and TRPM7-Dkinase, were fully suppressible by NS8592. Finally, we found that the benzimidazole group is required for the action of NS8593 on TRPM7. Taken together, our findings suggest that NS8593 may inhibit TRPM7 currents in Mg²⁺-dependent mode due to a direct interaction of its benzimidazole group with the pore-forming segment of TRPM7.