3NCZ

X-Ray Co-structure of Rho-Associated Protein Kinase (ROCK1) with a potent 2H-isoquinolin-1-one inhibitor

Summary for 3NCZ

• Entry DOI: 10.2210/pdb3ncz/pdb
• Related: 3NDM
• Descriptor: Rho-associated protein kinase 1, cis-4-amino-N-(7-chloro-1-oxo-1,2-dihydroisoquinolin-6-yl)cyclohexanecarboxamide (3 entities in total)
• Functional Keywords: rho kinase, dimer, phosphorylation, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 193328.28

Authors

Li, X. (deposition date: 2010-06-06, release date: 2010-12-08, Last modification date: 2024-02-21)

Primary citation

Ginn, J.D.,Bosanac, T.,Chen, R.,Cywin, C.,Hickey, E.,Kashem, M.,Kerr, S.,Kugler, S.,Li, X.,Prokopowicz, A.,Schlyer, S.,Smith, J.D.,Turner, M.R.,Wu, F.,Young, E.R.
Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: Part 2, optimization for blood pressure reduction in spontaneously hypertensive rats.
Bioorg.Med.Chem.Lett., 20:5153-5156, 2010

PubMed Abstract: Phenylglycine substituted isoquinolones 1 and 2 have previously been described as potent dual ROCK1/ROCK2 inhibitors. Here we describe the further SAR of this series to improve metabolic stability and rat oral exposure. Piperidine analog 20 which demonstrates sustained blood pressure normalization in an SHR blood pressure reduction model was identified through this effort.

PubMed: 20678931
DOI: 10.1016/j.bmcl.2010.07.014

Experimental method

X-RAY DIFFRACTION (3 Å)