5BML

ROCK 1 bound to a pyridine thiazole inhibitor

5BML の概要

• エントリーDOI: 10.2210/pdb5bml/pdb
• 分子名称: Rho-associated protein kinase 1, N-[4-(2-fluoropyridin-4-yl)thiophen-2-yl]-2-{3-[(methylsulfonyl)amino]phenyl}acetamide (3 entities in total)
• 機能のキーワード: kinase, dimer, dimerization, myosin, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: Q13464
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96835.50

構造登録者

Jacobs, M.D. (登録日: 2015-05-22, 公開日: 2015-06-10, 最終更新日: 2024-03-06)

主引用文献

Green, J.,Cao, J.,Bandarage, U.K.,Gao, H.,Court, J.,Marhefka, C.,Jacobs, M.,Taslimi, P.,Newsome, D.,Nakayama, T.,Shah, S.,Rodems, S.
Design, Synthesis, and Structure-Activity Relationships of Pyridine-Based Rho Kinase (ROCK) Inhibitors.
J.Med.Chem., 58:5028-5037, 2015

PubMed Abstract: The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction. Beginning with compound 4, an inhibitor of ROCK1 identified through high-throughput screening, systematic exploration of SAR, and application of structure-based design, led to potent and selective ROCK inhibitors. Compound 37 represents significant improvements in inhibition potency, kinase selectivity, and CYP inhibition and possesses pharmacokinetics suitable for in vivo experimentation.

PubMed: 26039570
DOI: 10.1021/acs.jmedchem.5b00424

実験手法

X-RAY DIFFRACTION (2.95 Å)