4W7P

Crystal Structure of ROCK 1 bound to YB-15-QD37

Summary for 4W7P

• Entry DOI: 10.2210/pdb4w7p/pdb
• Descriptor: Rho-associated protein kinase 1, N~1~-[2-(1H-indazol-5-yl)pyrido[3,4-d]pyrimidin-4-yl]-2-methylpropane-1,2-diamine (3 entities in total)
• Functional Keywords: inhibitor, kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: Q13464
• Total number of polymer chains: 4
• Total formula weight: 190839.59

Authors

Sprague, E.R. (deposition date: 2014-08-22, release date: 2014-10-15, Last modification date: 2023-12-27)

Primary citation

Shaw, D.,Hollingworth, G.,Soldermann, N.,Sprague, E.,Schuler, W.,Vangrevelinghe, E.,Duggan, N.,Thomas, M.,Kosaka, T.,Waters, N.,van Eis, M.J.
Novel ROCK inhibitors for the treatment of pulmonary arterial hypertension.
Bioorg.Med.Chem.Lett., 24:4812-4817, 2014

PubMed Abstract: A novel class of selective inhibitors of ROCK1 and ROCK2 has been identified by structural based drug design. PK/PD experiments using a set of highly selective Rho kinase inhibitors suggest that systemic Rho kinase inhibition is linked to a reversible reduction in lymphocyte counts. These results led to the consideration of topical delivery of these molecules, and to the identification of a lead molecule 7 which shows promising PK and PD in a murine model of pulmonary hypertension after intra-tracheal dosing.

PubMed: 25248678
DOI: 10.1016/j.bmcl.2014.09.002

Experimental method

X-RAY DIFFRACTION (2.8 Å)