8B75
CRYSTAL STRUCTURE OF HUMAN SOLUBLE ADENYLYL CYCLASE IN COMPLEX WITH THE INHIBITOR TDI-011861
Summary for 8B75
| Entry DOI | 10.2210/pdb8b75/pdb |
| Descriptor | Adenylate cyclase type 10, [(3~{R})-4-[2-[2-[[3-(2-azanyl-6-chloranyl-pyrimidin-4-yl)-1-[bis(fluoranyl)methyl]pyrazol-4-yl]methyl]phenoxy]ethyl]morpholin-3-yl]methanol (3 entities in total) |
| Functional Keywords | soluble adenylyl cyclase, adcy10, signaling enzyme, class iii cyclase, signaling protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 54764.59 |
| Authors | Steegborn, C.,Kehr, M. (deposition date: 2022-09-28, release date: 2023-03-29, Last modification date: 2024-11-20) |
| Primary citation | Miller, M.,Rossetti, T.,Ferreira, J.,Ghanem, L.,Balbach, M.,Kaur, N.,Levin, L.R.,Buck, J.,Kehr, M.,Coquille, S.,van den Heuvel, J.,Steegborn, C.,Fushimi, M.,Finkin-Groner, E.,Myers, R.W.,Kargman, S.,Liverton, N.J.,Huggins, D.J.,Meinke, P.T. Design, Synthesis, and Pharmacological Evaluation of Second-Generation Soluble Adenylyl Cyclase (sAC, ADCY10) Inhibitors with Slow Dissociation Rates. J.Med.Chem., 65:15208-15226, 2022 Cited by PubMed Abstract: 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 evaluation of diverse sAC pharmacology. PubMed: 36346696DOI: 10.1021/acs.jmedchem.2c01133 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.82 Å) |
Structure validation
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