生物活性

• 描述Soluble adenylate cyclase (sAC) is a non-plasma membrane bound form of adenylate cyclase (AC) that produces the second messenger adenosine 3',5'-cyclic AMP (cAMP) from ATP. It has been suggested to be involved in various cellular and physiological processes. KH 7, working as a classical uncoupler, is a sAC-specific inhibitor with an IC₅₀ of 2.7 μM. KH 7 at 25 μM inhibited ATP production by reducing respiration at lower concentrations and by perturbing membrane potential at higher concentrations in isolated mouse liver mitochondria^[2]. Application of the KH 7 showed almost complete inhibition of ATP-induced [Ca²⁺]_i elevation in pretreated EA.hy926 cells indicating it reduces intracellular Ca²⁺ response^[3]. In vivo, KH 7 (1.25 mM dissolved in 4 mL/kg DMSO) treatment caused an increased IOP (intraocular pressure) in avertin- and KXA(ketamine/xylazine/acepromazine)-anesthetized C57BL/6J mice compared with DMSO controls. In mice, KH 7 (5 μM) decreased outflow facility by 85.1% in nonanesthetized, enucleated eyes^[4].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00035490	Arrhythmia	Phase 3	Completed	-	-
  NCT03127059	Dysfunctional Breathing in Ast... more >>hma Collapse <<	Not Applicable	Recruiting	November 2020	Denmark ... more >> Dep. of Physiotherapy and Dep. of Pulmonology Recruiting Silkeborg, Central Denmark Region, Denmark, 8600 Contact: Karen H Andreasson       khad@regionsjaelland.dk    Dep. of Physiotherapy and Dep. of Pulmonology Recruiting Bispebjerg, Danish Capital Region, Denmark Contact: Karen H Andreasson       khad@regionsjaelland.dk    Allergi og Lungeklinikken Helsingør Recruiting Helsingør, Danish Capital Region, Denmark, 3000 Contact: Karen H Andreasson       khad@regionsjaelland.dk    Dep. of Physiotherapy and Dep. of Pulmonology Recruiting Hvidovre, Danish Capital Region, Denmark Contact: Karen H Andreasson       khad@regionsjaelland.dk    Dep. of Physiotherapy and Dep. of Pulmonology Recruiting Aalborg, Region North, Denmark Contact: Karen H Andreasson       khad@regionsjaelland.dk    Dep. of Physiotherapy and Dep. of Pulmonology Recruiting Naestved, Region Zealand, Denmark Contact: Karen H Andreasson, PT MSc    +45 24 25 49 26    khad@regionsjaelland.dk    Contact: Uffe Bødtger, MD PhD    +45 56 51 45 92    ubt@regionsjaelland.dk    Dep. of Physiotherapy and Dep. of Pulmonology Recruiting Roskilde, Region Zealand, Denmark Contact: Karen H Andreasson       khad@regionsjaelland.dk Collapse <<
  NCT03616912	Systemic Lupus Erythematosus	Phase 3	Recruiting	February 16, 2021	-

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• 参考文献

• [2] Jakobsen E, et al. The inhibitors of soluble adenylate cyclase 2-OHE, KH7, and bithionol compromise mitochondrial ATP production by distinct mechanisms. Biochem Pharmacol. 2018 Sep;155:92-101

  [3] Mewes M, et al. Soluble adenylyl cyclase (sAC) regulates calcium signaling in the vascular endothelium. FASEB J. 2019 Dec;33(12):13762-13774

  [4] Gandhi JK, et al. Differential Intraocular Pressure Measurements by Tonometry and Direct Cannulation After Treatment with Soluble Adenylyl Cyclase Inhibitors. J Ocul Pharmacol Ther. 2017 Oct;33(8):574-581