biostudies-literatureStrobbe DFIRB-Research Grant Consolidator Grant 2Italian Ministry of HealthEuropean Research CouncilAIRC-MFAG 21903Petplan Charitable TrustLAM-Bighi Grant InitiativeBiotechnology and Biological Sciences Research Council298-311https://www.ebi.ac.uk/biostudies/studies/S-EPMC9328437biostudies-literatureUnknown178(2)<h4>Background and purpose</h4>The mitochondrial F₁ F_o -ATPsynthase is pivotal for cellular homeostasis. When respiration is perturbed, its mode of action everts becoming an F₁ F_o -ATPase and therefore consuming rather producing ATP. Such a reversion is an obvious target for pharmacological intervention to counteract pathologies. Despite this, tools to selectively inhibit the phases of ATP hydrolysis without affecting the production of ATP remain scarce. Here, we report on a newly synthesised chemical, the NH-sulfoximine (NHS), which achieves such a selectivity.<h4>Experimental approach</h4>The chemical structure of the F₁ F_o -ATPase inhibitor BTB-06584 was used as a template to synthesise NHS. We assessed its pharmacology iBritish journal of pharmacologyNH-sulfoximine: A novel pharmacological inhibitor of the mitochondrial F₁ F_o -ATPase, which suppresses viability of cancerous cells.PMC9328437RBFR13P392IFO14/01/R/52BB/N007042/1COG 2018-819600_FIRMBB/M010384/1Strobbe DMontesano CFaccenda DPecorari RMinutolo AWiezorek SHendriks CMMConte OAbeti RCampanella MBolm CfalseNH-sulfoximine: A novel pharmacological inhibitor of the mitochondrial F₁ F_o -ATPase, which suppresses viability of cancerous cells.<h4>Background and purpose</h4>The mitochondrial F₁ F_o -ATPsynthase is pivotal for cellular homeostasis. When respiration is perturbed, its mode of action everts becoming an F₁ F_o -ATPase and therefore consuming rather producing ATP. Such a reversion is an obvious target for pharmacological intervention to counteract pathologies. Despite this, tools to selectively inhibit the phases of ATP hydrolysis without affecting the production of ATP remain scarce. Here, we report on a newly synthesised chemical, the NH-sulfoximine (NHS), which achieves such a selectivity.<h4>Experimental approach</h4>The chemical structure of the F₁ F_o -ATPase inhibitor BTB-06584 was used as a template to synthesise NHS. We assessed its pharmacology i2021-01-01T00:00:00Z2021 Jan2026-07-14T17:37:47.571Z2025-04-05T08:55:40.943ZS-EPMC93284373303761810.1111/bph.15279