5HVU

Rho-associated protein kinase 1 (ROCK 1) in complex with a pyridine thiazole piperidine inhibitor

Summary for 5HVU

• Entry DOI: 10.2210/pdb5hvu/pdb
• Descriptor: Rho-associated protein kinase 1, 2-{3-[3-(piperidin-4-yl)propoxy]phenyl}-N-[4-(pyridin-4-yl)-1,3-thiazol-2-yl]acetamide (3 entities in total)
• Functional Keywords: kinase, inhibitor, complex, solubilizing group, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 96897.71

Authors

Jacobs, M.J. (deposition date: 2016-01-28, release date: 2017-02-08, Last modification date: 2023-09-27)

Primary citation

Gao, H.,Marhefka, C.,Jacobs, M.D.,Cao, J.,Bandarage, U.K.,Green, J.
ROCK inhibitors 2. Improving potency, selectivity and solubility through the application of rationally designed solubilizing groups.
Bioorg. Med. Chem. Lett., 2018

PubMed Abstract: Solubilizing groups have been frequently appended to kinase inhibitor drug molecules when solubility is insufficient for pharmaceutical development. Such groups are usually located at substitution sites that have minimal impact on target activity. In this report we describe the incorporation of solubilizing groups in a class of Rho kinase (ROCK) inhibitors that not only confer improved solubility, but also enhance target potency and selectivity against a closely related kinase, PKA.

PubMed: 29945794
DOI: 10.1016/j.bmcl.2018.06.043

Experimental method

X-RAY DIFFRACTION (2.8 Å)