3R22

Design, synthesis, and biological evaluation of pyrazolopyridine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (Part I)

3R22 の概要

• エントリーDOI: 10.2210/pdb3r22/pdb
• 関連するPDBエントリー: 3R21
• 分子名称: Serine/threonine-protein kinase 6, N-{5-[(1-cycloheptyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino]pyridin-2-yl}methanesulfonamide (3 entities in total)
• 機能のキーワード: kinase domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton, centrosome: O14965
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31748.42

構造登録者

Zhang, L.,Fan, J.,Chong, J.-H.,Cesana, A.,Tam, B.,Gilson, C.,Boykin, C.,Wang, D.,Marcotte, D.,Le Brazidec, J.-Y.,Aivazian, D.,Piao, J.,Lundgren, K.,Hong, K.,Vu, K.,Nguyen, K. (登録日: 2011-03-11, 公開日: 2011-08-10, 最終更新日: 2023-09-13)

主引用文献

Zhang, L.,Fan, J.,Chong, J.H.,Cesena, A.,Tam, B.Y.,Gilson, C.,Boykin, C.,Wang, D.,Aivazian, D.,Marcotte, D.,Xiao, G.,Le Brazidec, J.Y.,Piao, J.,Lundgren, K.,Hong, K.,Vu, K.,Nguyen, K.,Gan, L.S.,Silvian, L.,Ling, L.,Teng, M.,Reff, M.,Takeda, N.,Timple, N.,Wang, Q.,Morena, R.,Khan, S.,Zhao, S.,Li, T.,Lee, W.C.,Taveras, A.G.,Chao, J.
Design, synthesis, and biological evaluation of pyrazolopyrimidine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (part I).
Bioorg.Med.Chem.Lett., 21:5633-5637, 2011

PubMed Abstract: A novel class of pyrazolopyrimidine-sulfonamides was discovered as selective dual inhibitors of aurora kinase A (AKA) and cyclin-dependent kinase 1 (CDK1). These inhibitors were originally designed based on an early lead (compound I). SAR development has led to the discovery of potent inhibitors with single digit nM IC(50)s towards both AKA and CDK1. An exemplary compound 1a has demonstrated good efficacy in an HCT116 colon cancer xenograft model.

PubMed: 21798738
DOI: 10.1016/j.bmcl.2011.06.129

実験手法

X-RAY DIFFRACTION (2.9 Å)