9D4X

Structure of PAK1 in complex with compound 16

これはPDB形式変換不可エントリーです。

9D4X の概要

• エントリーDOI: 10.2210/pdb9d4x/pdb
• 分子名称: Serine/threonine-protein kinase PAK 1, N~2~-{[(1R,3R,4S)-4-amino-3-(3-chlorophenyl)cyclohexyl]methyl}-N~4~-(5-cyclopropyl-1,3-thiazol-2-yl)pyrimidine-2,4-diamine (3 entities in total)
• 機能のキーワード: serine/threonine-protein kinase, transferase, inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67308.42

構造登録者

Dementiev, A.,Suto, R.K.,Olland, A.M. (登録日: 2024-08-13, 公開日: 2025-04-02, 最終更新日: 2025-06-25)

主引用文献

Johns, D.M.,Olejniczak, J.,Babbar, A.,Boone, C.D.,Cakici, O.,Cheng, M.,Cheng, Q.Q.,Dementiev, A.,Eick, M.,Ferdyan, N.,Fontano, E.,Forman, A.,Kozlowski, R.,Lee, S.W.,Mehta, S.,Mowery, K.,Murray, B.,Nguyen, V.,Olland, A.,Phan, K.,Rivera, L.,Sabat, M.,Sprengeler, P.,Srinivasan, K.,Sun, Z.,Suto, R.K.,Wilkinson, T.,Wang, C.,Yu, N.,Xu, M.,Goel, V.,Hirst, G.,Reich, S.
Identification of a p21-activated kinase 1 (PAK1) inhibitor with 10-fold selectivity against PAK2.
Bioorg.Med.Chem.Lett., :130307-130307, 2025

PubMed Abstract: The p21-activated kinases (PAKs) are noted for their role in cytoskeletal organization, cellular morphogenesis, and pro-survival signaling. PAK1 is of particular interest due to its role in tumorigenesis, being amplified in multiple cancers (the most prevalent being breast, ovarian, and melanoma cancers). PAK2 is closely related to PAK1 in structure but is associated with cardiotoxicity. A structure-based design effort targeting a PAK1 (over PAK2) selective small molecule inhibitor is detailed herein. We report here the first crystal structure of PAK2 and use this crystal structure to design a PAK1 inhibitor with ten-fold selectivity over PAK2.

PubMed: 40516764
DOI: 10.1016/j.bmcl.2025.130307

実験手法

X-RAY DIFFRACTION (1.847 Å)