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NH125 is a synthetic small molecule originally discovered as an antibacterial agent active against both Gram-positive and Gram-negative bacteria, primarily via inhibition of histidine protein kinases[5][15][7]. It was later found to be a potent and selective inhibitor of eukaryotic elongation factor-2 kinase (eEF-2K), with an IC50 of approximately 60 nM for eEF-2K[1][13][16]. In mammalian cells, NH125 demonstrates anticancer properties, inducing cell death and inhibiting cell proliferation across a broad range of human cancer cell lines via multiple pathways including inhibition of eEF-2K, induction of eEF2 phosphorylation, and activation of integrated stress response and GADD45 pathways[3][5][14]. NH125 disrupts bacterial membranes and kills persistent cells, such as methicillin-resistant Staphylococcus aureus (MRSA) persisters, and sensitizes S. aureus to cell wall-targeting antibiotics by inhibiting the VraS histidine kinase[2][4]. It also inhibits protein kinase C, protein kinase A, and calmodulin-dependent kinase II at higher concentrations[1][13]. The compound has demonstrated efficacy in vitro and in vivo against cancer and bacterial models, but is currently used primarily as a research tool and is not approved for clinical use.
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