4YJN

Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii (TgCDPK1) in complex with inhibitor UW1639

4YJN の概要

• エントリーDOI: 10.2210/pdb4yjn/pdb
• 関連するPDBエントリー: 4ONA
• 分子名称: Calmodulin-domain protein kinase 1, 5-amino-1-tert-butyl-3-[2-(cyclobutyloxy)quinolin-6-yl]-1H-pyrazole-4-carboxamide (3 entities in total)
• 機能のキーワード: serine/threonine protein kinase, transferase, calcium-binding, atp-binding, bumped kinase inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Toxoplasma gondii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 55606.37

構造登録者

Merritt, E.A. (登録日: 2015-03-03, 公開日: 2015-11-25, 最終更新日: 2023-09-27)

主引用文献

Huang, W.,Ojo, K.K.,Zhang, Z.,Rivas, K.,Vidadala, R.S.,Scheele, S.,DeRocher, A.E.,Choi, R.,Hulverson, M.A.,Barrett, L.K.,Bruzual, I.,Siddaramaiah, L.K.,Kerchner, K.M.,Kurnick, M.D.,Freiberg, G.M.,Kempf, D.,Hol, W.G.,Merritt, E.A.,Neckermann, G.,de Hostos, E.L.,Isoherranen, N.,Maly, D.J.,Parsons, M.,Doggett, J.S.,Van Voorhis, W.C.,Fan, E.
SAR Studies of 5-Aminopyrazole-4-carboxamide Analogues as Potent and Selective Inhibitors of Toxoplasma gondii CDPK1.
Acs Med.Chem.Lett., 6:1184-1189, 2015

PubMed Abstract: We previously discovered compounds based on a 5-aminopyrazole-4-carboxamide scaffold to be potent and selective inhibitors of CDPK1 from . The current work, through structure-activity relationship studies, led to the discovery of compounds ( and ) with improved characteristics over the starting inhibitor in terms of solubility, plasma exposure after oral administration in mice, or efficacy on parasite growth inhibition. Compounds and were further demonstrated to be more effective than in a mouse infection model and markedly reduced the amount of in the brain, spleen, and peritoneal fluid, and given at 20 mg/kg eliminated from the peritoneal fluid.

PubMed: 26693272
DOI: 10.1021/acsmedchemlett.5b00319

実験手法

X-RAY DIFFRACTION (2.6 Å)