8B75

CRYSTAL STRUCTURE OF HUMAN SOLUBLE ADENYLYL CYCLASE IN COMPLEX WITH THE INHIBITOR TDI-011861

8B75 の概要

• エントリーDOI: 10.2210/pdb8b75/pdb
• 分子名称: 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)
• 機能のキーワード: soluble adenylyl cyclase, adcy10, signaling enzyme, class iii cyclase, signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 54764.59

構造登録者

Steegborn, C.,Kehr, M. (登録日: 2022-09-28, 公開日: 2023-03-29, 最終更新日: 2024-11-20)

主引用文献

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

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: 36346696
DOI: 10.1021/acs.jmedchem.2c01133

実験手法

X-RAY DIFFRACTION (1.82 Å)