5BML

ROCK 1 bound to a pyridine thiazole inhibitor

Summary for 5BML

• Entry DOI: 10.2210/pdb5bml/pdb
• Descriptor: Rho-associated protein kinase 1, N-[4-(2-fluoropyridin-4-yl)thiophen-2-yl]-2-{3-[(methylsulfonyl)amino]phenyl}acetamide (3 entities in total)
• Functional Keywords: kinase, dimer, dimerization, myosin, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: Q13464
• Total number of polymer chains: 2
• Total formula weight: 96835.50

Authors

Jacobs, M.D. (deposition date: 2015-05-22, release date: 2015-06-10, Last modification date: 2024-03-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.95 Å)