8b75: Difference between revisions
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8b75 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b75 OCA], [https://pdbe.org/8b75 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b75 RCSB], [https://www.ebi.ac.uk/pdbsum/8b75 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b75 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8b75 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b75 OCA], [https://pdbe.org/8b75 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b75 RCSB], [https://www.ebi.ac.uk/pdbsum/8b75 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b75 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | |||
[https://www.uniprot.org/uniprot/ADCYA_HUMAN ADCYA_HUMAN] Idiopathic hypercalciuria. Disease susceptibility is associated with variations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ADCYA_HUMAN ADCYA_HUMAN] Soluble adenylyl cyclase that has a critical role in mammalian spermatogenesis. Produces the cAMP which mediates in part the cAMP-responsive nuclear factors indispensable for maturation of sperm in the epididymis. Induces capacitation, the maturational process that sperm undergo prior to fertilization. May be the bicarbonate sensor. Involved in ciliary beat regulation.<ref>PMID:15659711</ref> <ref>PMID:17591988</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Soluble adenylyl cyclase (sAC: ADCY10) is an enzyme involved in intracellular signaling. Inhibition of sAC has potential therapeutic utility in a number of areas. For example, sAC is integral to successful male fertility: sAC activation is required for sperm motility and ability to undergo the acrosome reaction, two processes central to oocyte fertilization. Pharmacologic evaluation of existing sAC inhibitors for utility as on-demand, nonhormonal male contraceptives suggested that both high intrinsic potency, fast on and slow dissociation rates are essential design elements for successful male contraceptive applications. During the course of the medicinal chemistry campaign described here, we identified sAC inhibitors that fulfill these criteria and are suitable for in vivo evaluation of diverse sAC pharmacology. | |||
Design, Synthesis, and Pharmacological Evaluation of Second-Generation Soluble Adenylyl Cyclase (sAC, ADCY10) Inhibitors with Slow Dissociation Rates.,Miller M, Rossetti T, Ferreira J, Ghanem L, Balbach M, Kaur N, Levin LR, Buck J, Kehr M, Coquille S, van den Heuvel J, Steegborn C, Fushimi M, Finkin-Groner E, Myers RW, Kargman S, Liverton NJ, Huggins DJ, Meinke PT J Med Chem. 2022 Nov 24;65(22):15208-15226. doi: 10.1021/acs.jmedchem.2c01133. , Epub 2022 Nov 8. PMID:36346696<ref>PMID:36346696</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 8b75" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 10:03, 21 November 2024
CRYSTAL STRUCTURE OF HUMAN SOLUBLE ADENYLYL CYCLASE IN COMPLEX WITH THE INHIBITOR TDI-011861CRYSTAL STRUCTURE OF HUMAN SOLUBLE ADENYLYL CYCLASE IN COMPLEX WITH THE INHIBITOR TDI-011861
Structural highlights
DiseaseADCYA_HUMAN Idiopathic hypercalciuria. Disease susceptibility is associated with variations affecting the gene represented in this entry. FunctionADCYA_HUMAN Soluble adenylyl cyclase that has a critical role in mammalian spermatogenesis. Produces the cAMP which mediates in part the cAMP-responsive nuclear factors indispensable for maturation of sperm in the epididymis. Induces capacitation, the maturational process that sperm undergo prior to fertilization. May be the bicarbonate sensor. Involved in ciliary beat regulation.[1] [2] Publication Abstract from PubMedSoluble adenylyl cyclase (sAC: ADCY10) is an enzyme involved in intracellular signaling. Inhibition of sAC has potential therapeutic utility in a number of areas. For example, sAC is integral to successful male fertility: sAC activation is required for sperm motility and ability to undergo the acrosome reaction, two processes central to oocyte fertilization. Pharmacologic evaluation of existing sAC inhibitors for utility as on-demand, nonhormonal male contraceptives suggested that both high intrinsic potency, fast on and slow dissociation rates are essential design elements for successful male contraceptive applications. During the course of the medicinal chemistry campaign described here, we identified sAC inhibitors that fulfill these criteria and are suitable for in vivo evaluation of diverse sAC pharmacology. Design, Synthesis, and Pharmacological Evaluation of Second-Generation Soluble Adenylyl Cyclase (sAC, ADCY10) Inhibitors with Slow Dissociation Rates.,Miller M, Rossetti T, Ferreira J, Ghanem L, Balbach M, Kaur N, Levin LR, Buck J, Kehr M, Coquille S, van den Heuvel J, Steegborn C, Fushimi M, Finkin-Groner E, Myers RW, Kargman S, Liverton NJ, Huggins DJ, Meinke PT J Med Chem. 2022 Nov 24;65(22):15208-15226. doi: 10.1021/acs.jmedchem.2c01133. , Epub 2022 Nov 8. PMID:36346696[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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