Submitted by jaf4002 on February 14, 2023 - 3:11pm
Title | Assessing potency and binding kinetics of soluble adenylyl cyclase (sAC) inhibitors to maximize therapeutic potential. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Rossetti T, Ferreira J, Ghanem L, Buck H, Steegborn C, Myers RW, Meinke PT, Levin LR, Buck J |
Journal | Front Physiol |
Volume | 13 |
Pagination | 1013845 |
Date Published | 2022 |
ISSN | 1664-042X |
Abstract | In mammalian cells, 10 different adenylyl cyclases produce the ubiquitous second messenger, cyclic adenosine monophosphate (cAMP). Amongst these cAMP-generating enzymes, bicarbonate (HCO3 -)-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 in vitro assays to identify and characterize sAC inhibitors for therapeutic use. The affinity and binding kinetics of an inhibitor can greatly influence in vivo efficacy, therefore, we developed improved assays for assessing these efficacy defining features. |
DOI | 10.3389/fphys.2022.1013845 |
Alternate Journal | Front Physiol |
PubMed ID | 36246105 |
PubMed Central ID | PMC9554468 |
Grant List | P50 HD100549 / HD / NICHD NIH HHS / United States R01 AG061290 / AG / NIA NIH HHS / United States R01 HD088571 / HD / NICHD NIH HHS / United States |