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.
KH 7是可溶性腺苷酸环化酶(sAC) 的特异性抑制剂，其对重组sAC蛋白的IC50约为 3-10 µM[1]。KH 7常用于精子活力、线粒体功能和细胞内cAMP信号传导的研究[2]。
将KH 7(10-50μM；1h)添加到野生型精子中，KH7在IC50为10μM浓度下抑制获能诱导的cAMP水平升高，在更高浓度(50μM)下，尽管KH 7浓度比其IC50高5到10倍，但KH 7对sAC（而非 tmAC）仍具有选择性，并显著降低精子中基础cAMP的积累[1]。KH 7可抑制线粒体内cAM 的产生，用该物质处理成纤维细胞培养物会导致成熟核编码的NDUFS4、NDUFV2和NDUFA9亚基（复合物I）的总量显著减少（35-50%）[2]。用KH 7(10-50μM；1h)处理人脐静脉内皮细胞可显著降低内皮细胞中的cAMP水平[3]。在稳定过表达sAC的 293T-HEK细胞中，用KH 7（10-50μM；1h）处理后，细胞呼吸作用增强、COX 活性增加和 ATP合成增加均受到显著抑制[4]。