7JOV

CRYSTAL STRUCTURE OF RHO-ASSOCIATED PROTEIN KINASE 2 (ROCK2) IN COMPLEX WITH A PHENYLPYRAZOLE AMIDE INHIBITOR

Summary for 7JOV

• Entry DOI: 10.2210/pdb7jov/pdb
• Descriptor: Rho-associated protein kinase 2, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, N-[(1S)-2-hydroxy-1-phenylethyl]-3-methoxy-4-(1H-pyrazol-4-yl)benzamide, ... (5 entities in total)
• Functional Keywords: rock1, kinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 8
• Total formula weight: 366400.97

Authors

Muckelbauer, J.K. (deposition date: 2020-08-07, release date: 2020-09-02, Last modification date: 2024-03-06)

Primary citation

Hu, Z.,Wang, C.,Glunz, P.W.,Li, J.,Cheadle, N.L.,Chen, A.Y.,Chen, X.Q.,Myers, J.E.,Guarino, V.R.,Rose, A.,Sack, J.S.,Sitkoff, D.,Taylor, D.S.,Xu, S.,Yan, C.,Zhang, H.,Zhang, L.,Hennan, J.,Adam, L.P.,Wexler, R.R.,Quan, M.L.
Discovery of a phenylpyrazole amide ROCK inhibitor as a tool molecule for in vivo studies.
Bioorg.Med.Chem.Lett., 30:127495-127495, 2020

PubMed Abstract: Structure-activity relationship optimization on a series of phenylpyrazole amides led to the identification of a dual ROCK1 and ROCK2 inhibitor (25) which demonstrated good potency, kinome selectivity and favorable pharmacokinetic profiles. Compound 25 was selected as a tool molecule for in vivo studies including evaluating hemodynamic effects in telemeterized mice, from which moderate decreases in blood pressure were observed.

PubMed: 32798651
DOI: 10.1016/j.bmcl.2020.127495

Experimental method

X-RAY DIFFRACTION (2.586 Å)