| Structural highlights
7ovd is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.2Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
ADCYA_HUMAN Idiopathic hypercalciuria. Disease susceptibility is associated with variations affecting the gene represented in this entry.
Function
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.[1] [2]
Publication Abstract from PubMed
Soluble adenylyl cyclase (sAC) has gained attention as a potential therapeutic target given the role of this enzyme in intracellular signaling. We describe successful efforts to design improved sAC inhibitors amenable for in vivo interrogation of sAC inhibition to assess its potential therapeutic applications. This work culminated in the identification of TDI-10229 (12), which displays nanomolar inhibition of sAC in both biochemical and cellular assays and exhibits mouse pharmacokinetic properties sufficient to warrant its use as an in vivo tool compound.
Discovery of TDI-10229: A Potent and Orally Bioavailable Inhibitor of Soluble Adenylyl Cyclase (sAC, ADCY10).,Fushimi M, Buck H, Balbach M, Gorovyy A, Ferreira J, Rossetti T, Kaur N, Levin LR, Buck J, Quast J, van den Heuvel J, Steegborn C, Finkin-Groner E, Kargman S, Michino M, Foley MA, Miller M, Liverton NJ, Huggins DJ, Meinke PT ACS Med Chem Lett. 2021 Jul 14;12(8):1283-1287. doi:, 10.1021/acsmedchemlett.1c00273. eCollection 2021 Aug 12. PMID:34413957[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Geng W, Wang Z, Zhang J, Reed BY, Pak CY, Moe OW. Cloning and characterization of the human soluble adenylyl cyclase. Am J Physiol Cell Physiol. 2005 Jun;288(6):C1305-16. Epub 2005 Jan 19. PMID:15659711 doi:http://dx.doi.org/10.1152/ajpcell.00584.2004
- ↑ Schmid A, Sutto Z, Nlend MC, Horvath G, Schmid N, Buck J, Levin LR, Conner GE, Fregien N, Salathe M. Soluble adenylyl cyclase is localized to cilia and contributes to ciliary beat frequency regulation via production of cAMP. J Gen Physiol. 2007 Jul;130(1):99-109. PMID:17591988 doi:http://dx.doi.org/jgp.200709784
- ↑ Fushimi M, Buck H, Balbach M, Gorovyy A, Ferreira J, Rossetti T, Kaur N, Levin LR, Buck J, Quast J, van den Heuvel J, Steegborn C, Finkin-Groner E, Kargman S, Michino M, Foley MA, Miller M, Liverton NJ, Huggins DJ, Meinke PT. Discovery of TDI-10229: A Potent and Orally Bioavailable Inhibitor of Soluble Adenylyl Cyclase (sAC, ADCY10). ACS Med Chem Lett. 2021 Jul 14;12(8):1283-1287. PMID:34413957 doi:10.1021/acsmedchemlett.1c00273
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