评估可溶性腺苷酸环化酶（sAC）抑制剂的效力和结合动力学以最大化治疗潜力。
Assessing potency and binding kinetics of soluble adenylyl cyclase (sAC) inhibitors to maximize therapeutic potential.
作者信息
Rossetti Thomas, Ferreira Jacob, Ghanem Lubna, Buck Hannes, Steegborn Clemens, Myers Robert W, Meinke Peter T, Levin Lonny R, Buck Jochen
机构信息
Department of Pharmacology, Weill Cornell Medicine, New York, NY, United States.
Department of Biochemistry, University of Bayreuth, Bayreuth, Germany.
出版信息
Front Physiol. 2022 Sep 28;13:1013845. doi: 10.3389/fphys.2022.1013845. eCollection 2022.
In mammalian cells, 10 different adenylyl cyclases produce the ubiquitous second messenger, cyclic adenosine monophosphate (cAMP). Amongst these cAMP-generating enzymes, bicarbonate (HCO )-regulated soluble adenylyl cyclase (sAC; ADCY10) is uniquely essential in sperm for reproduction. For this reason, sAC has been proposed as a potential therapeutic target for non-hormonal contraceptives for men. Here, we describe key sAC-focused assays to identify and characterize sAC inhibitors for therapeutic use. The affinity and binding kinetics of an inhibitor can greatly influence efficacy, therefore, we developed improved assays for assessing these efficacy defining features.
在哺乳动物细胞中，10种不同的腺苷酸环化酶产生普遍存在的第二信使环磷酸腺苷（cAMP）。在这些产生cAMP的酶中，碳酸氢盐（HCO ）调节的可溶性腺苷酸环化酶（sAC；ADCY10）在精子繁殖过程中具有独特的重要性。因此，sAC已被提议作为男性非激素避孕药的潜在治疗靶点。在此，我们描述了以sAC为重点的关键检测方法，以鉴定和表征用于治疗的sAC抑制剂。抑制剂的亲和力和结合动力学可极大地影响疗效，因此，我们开发了改进的检测方法来评估这些决定疗效的特征。
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