3NDM

Crystal structure of Rho-Associated Protein Kinase (ROCK1) with a potent isoquinolone derivative


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.310 
  • R-Value Work: 0.241 
  • R-Value Observed: 0.244 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: part 3, aryl substituted pyrrolidines.

Bosanac, T.Hickey, E.R.Ginn, J.Kashem, M.Kerr, S.Kugler, S.Li, X.Olague, A.Schlyer, S.Young, E.R.

(2010) Bioorg Med Chem Lett 20: 3746-3749

  • DOI: https://doi.org/10.1016/j.bmcl.2010.04.069
  • Primary Citation of Related Structures:  
    3NDM

  • PubMed Abstract: 

    The discovery and SAR of a series of beta-aryl substituted pyrrolidine 2H-isoquinolin-1-one inhibitors of Rho-kinase (ROCK) derived from 2 is herein described. SAR studies have shown that aryl groups in the beta-position are optimal for potency. Our efforts focused on improving the ROCK potency of this isoquinolone class of inhibitors which led to the identification of pyrrolidine 32 which demonstrated a 10-fold improvement in aortic ring (AR) potency over 2.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Boehringer-Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877-0368, USA. todd.bosanac@boehringer-ingelheim.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Rho-Associated Protein Kinase (ROCK1)
A, B, C, D
415Homo sapiensMutation(s): 0 
EC: 2.7.1.37
UniProt & NIH Common Fund Data Resources
Find proteins for Q13464 (Homo sapiens)
Explore Q13464 
Go to UniProtKB:  Q13464
PHAROS:  Q13464
GTEx:  ENSG00000067900 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13464
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3ND
Query on 3ND

Download Ideal Coordinates CCD File 
E [auth B],
F [auth C],
G [auth D]
(3S,4R)-N-(7-chloro-1-oxo-1,4-dihydroisoquinolin-6-yl)-4-(4-chlorophenyl)pyrrolidine-3-carboxamide
C20 H17 Cl2 N3 O2
WWMMSIAGRVSGLG-JKSUJKDBSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
3ND PDBBind:  3NDM IC50: 11 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.310 
  • R-Value Work: 0.241 
  • R-Value Observed: 0.244 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 162.784α = 90
b = 83.553β = 119.95
c = 177.962γ = 90
Software Package:
Software NamePurpose
d*TREKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
MAR345dtbdata collection
d*TREKdata reduction
CNXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2010-12-08 
  • Deposition Author(s): Li, X.

Revision History  (Full details and data files)

  • Version 1.0: 2010-12-08
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations