9HFP

ROCK2 IN COMPLEX WITH CPD7

これはPDB形式変換不可エントリーです。

9HFP の概要

• エントリーDOI: 10.2210/pdb9hfp/pdb
• 分子名称: Rho-associated protein kinase 2, ~{N}-[4-[(3~{R})-piperidin-3-yl]oxyphenyl]-1~{H}-pyrrolo[2,3-b]pyridin-4-amine (2 entities in total)
• 機能のキーワード: kinase, complex structure, inhibitor, transferase
• 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: 45780.10

構造登録者

Scheufler, C.,Griessner, A. (登録日: 2024-11-18, 公開日: 2025-07-09, 最終更新日: 2025-07-23)

主引用文献

Namoto, K.,Vangrevelinghe, E.,Machauer, R.,Behnke, D.,Buschmann, N.,Lachal, J.,Schipp, K.,Sorge, M.,Barker, K.,Fabbiani, F.,Piechon, P.,Connor, L.E.,Laurent, S.,Lohmann, F.,Unterreiner, V.,George, E.L.,Redmond, E.,Wang, L.,Scheufler, C.,Sohal, B.,Sailer, A.W.,Glatthar, R.,Tchorz, J.S.,Maibaum, J.
Discovery and Optimization of Selective Inhibitors of Large Tumor Suppressor Kinases LATS1 and 2 for In Vivo Investigation of the Hippo-YAP Pathway in Tissue Regeneration.
J.Med.Chem., 68:13591-13608, 2025

PubMed Abstract: Large Tumor Suppressor kinases LATS1 and 2 (LATS1/2) are serine/threonine kinases and core regulators of the Hippo-YAP pathway. Inhibition of LATS1/2 promotes nuclear translocation of nonphosphorylated YAP, thereby initiating a downstream cascade promoting cell proliferation. We set out to investigate the potential of LATS inhibition as a therapeutic approach to enhance tissue regeneration and hereby report a structure-guided optimization of screening hit for potency, binding efficiency, and physicochemical properties, leading to a highly selective, cellularly active, and orally available tool compound (NIBR-LTSi) that demonstrated target engagement and in vivo YAP target gene activation in rodents.

PubMed: 40574495
DOI: 10.1021/acs.jmedchem.5c00350

実験手法

X-RAY DIFFRACTION (2.92 Å)