KH 7

KH 7 is a specific inhibitor of soluble adenylyl cyclase (sAC) with an IC₅₀ of approximately 3-10µM against recombinant sAC protein ^[1]. This compound is commonly used in studies of sperm motility, mitochondrial function, and intracellular cAMP signaling ^[2].

KH 7 (10-50μM; 1h) was added to wild-type sperm and inhibited the capacitation-induced increase in cAMP levels at a KH7 concentration with an IC₅₀ of 10μM. At a higher concentration (50μM), KH 7 was selective for sAC (but not tmAC), despite concentrations 5- to 10-fold higher than its IC₅₀, and significantly reduced basal cAMP accumulation in sperm^[1]. Treatment of fibroblast cultures with KH 7, which inhibits intramitochondrial production of cAMP, causes a marked (35-50%) decrease of the overall amount of the mature forms of the nuclear-encoded NDUFS4, NDUFV2 and NDUFA9 subunits of complex I ^[2]. Treatment of human umbilical vein endothelial cells (HUVECs) with KH 7 (10µM) for 1 hour significantly reduced cellular cAMP levels in the endothelial cells ^[3]. In 293T-HEK cells stably overexpressing sAC and treated with KH 7(25μM; 1h), there was significant inhibition of enhanced respiration, increased COX activity, and elevated ATP synthesis^[4].

References:
[1]. De Rasmo D, Signorile A, Santeramo A, et al. Intramitochondrial adenylyl cyclase controls the turnover of nuclear-encoded subunits and activity of mammalian complex I of the respiratory chain[J]. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2015, 1853(1): 183-191.
[2]. Chen M, Yi L, Jin X, et al. Resveratrol attenuates vascular endothelial inflammation by inducing autophagy through the cAMP signaling pathway[J]. Autophagy, 2013, 9(12): 2033-2045.
[3]. Hess K C, Jones B H, Marquez B, et al. The “soluble” adenylyl cyclase in sperm mediates multiple signaling events required for fertilization[J]. Developmental cell, 2005, 9(2): 249-259.
[4]. Acin-Perez R, Salazar E, Kamenetsky M, et al. Cyclic AMP produced inside mitochondria regulates oxidative phosphorylation[J]. Cell metabolism, 2009, 9(3): 265-276.