4YVE

ROCK 1 bound to methoxyphenyl thiazole inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.40 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.219 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Design, Synthesis, and Structure-Activity Relationships of Pyridine-Based Rho Kinase (ROCK) Inhibitors.

Green, J.Cao, J.Bandarage, U.K.Gao, H.Court, J.Marhefka, C.Jacobs, M.Taslimi, P.Newsome, D.Nakayama, T.Shah, S.Rodems, S.

(2015) J Med Chem 58: 5028-5037

  • DOI: https://doi.org/10.1021/acs.jmedchem.5b00424
  • Primary Citation of Related Structures:  
    4YVC, 4YVE, 5BML

  • PubMed Abstract: 

    The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction. Beginning with compound 4, an inhibitor of ROCK1 identified through high-throughput screening, systematic exploration of SAR, and application of structure-based design, led to potent and selective ROCK inhibitors. Compound 37 represents significant improvements in inhibition potency, kinase selectivity, and CYP inhibition and possesses pharmacokinetics suitable for in vivo experimentation.


  • Organizational Affiliation

    †Vertex Pharmaceuticals, Inc., 50 Northern Avenue, Boston, Massachusetts 02210, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Rho-associated protein kinase 1
A, B
415Homo sapiensMutation(s): 0 
Gene Names: ROCK1
EC: 2.7.11.1
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
4KK
Query on 4KK

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
2-(3-methoxyphenyl)-N-[4-(pyridin-4-yl)-1,3-thiazol-2-yl]acetamide
C17 H15 N3 O2 S
GOPDRFODUBCWMB-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
4KK BindingDB:  4YVE Ki: min: 83, max: 100 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.40 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.219 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 181.98α = 90
b = 181.98β = 90
c = 90.56γ = 120
Software Package:
Software NamePurpose
d*TREKdata reduction
d*TREKdata scaling
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2015-06-10 
  • Deposition Author(s): Jacobs, M.D.

Revision History  (Full details and data files)

  • Version 1.0: 2015-06-10
    Type: Initial release
  • Version 1.1: 2015-06-17
    Changes: Database references
  • Version 1.2: 2015-07-08
    Changes: Data collection
  • Version 1.3: 2018-07-18
    Changes: Data collection, Database references, Derived calculations, Source and taxonomy
  • Version 1.4: 2023-09-27
    Changes: Data collection, Database references, Refinement description