Ru265 is a non-cytotoxic, aqueous soluble nitrido-bridged dinuclear Ru(IV) complex th at acts as a selective mitochondrial calcium uniporter (MCU) inhibitor via a manner distinct from the oxo-bridged Ru360. Ru265 selectively reduces 100 μM histamine-induced mitochondrial [Ca2+] (mCa2+), but not cytosolic [Ca2+] (cCa2+) transient (50 ?M; HeLa) by blocking MCU-mediated mCa2+ uptake at a >10-fold greater potency as Ru360 (IC50 ~2.6 nM vs. 30 nM; HEK293T) without effecting mCa2+ efflux or membrane potential (ΔΨm). Ru265 (50 μM) protects neonatal r at ventricular myocytes from hypoxia/reoxygenation injury by preventing mPTP opening and mCa2+ overload.
