5BVE

Tetrahydropyrrolo-diazepenones as inhibitors of ERK2 kinase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.175 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Tetrahydropyrrolo-diazepenones as inhibitors of ERK2 kinase.

Bagdanoff, J.T.Jain, R.Han, W.Zhu, S.Madiera, A.M.Lee, P.S.Ma, X.Poon, D.

(2015) Bioorg Med Chem Lett 25: 3788-3792

  • DOI: https://doi.org/10.1016/j.bmcl.2015.07.091
  • Primary Citation of Related Structures:  
    5BVD, 5BVE, 5BVF

  • PubMed Abstract: 

    A series of structure based drug design hypotheses and focused screening efforts led to the identification of tetrahydropyrrolo-diazepenones with striking potency against ERK2 kinase. The role of fluorination in mitigating microsomal clearance was systematically explored. Ultimately, it was found that fluorination of a cyclopentanol substructure provided significant improvement in both potency and human metabolic stability.


  • Organizational Affiliation

    Global Discovery Chemistry/Oncology and Exploratory Chemistry, Novartis Institutes for BioMedical Research, 250 Massachusetts Ave., Cambridge, MA 02139, USA. Electronic address: jeffrey.bagdanoff@novartis.com.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mitogen-activated protein kinase 1361Homo sapiensMutation(s): 0 
Gene Names: MAPK1ERK2PRKM1PRKM2
EC: 2.7.11.24
UniProt & NIH Common Fund Data Resources
Find proteins for P28482 (Homo sapiens)
Explore P28482 
Go to UniProtKB:  P28482
PHAROS:  P28482
GTEx:  ENSG00000100030 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28482
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
4VG Binding MOAD:  5BVE IC50: 1.00e-2 (nM) from 1 assay(s)
BindingDB:  5BVE IC50: 1.00e-2 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.175 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.242α = 90
b = 70.672β = 90
c = 120.307γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PROCESSdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-09-09
    Type: Initial release
  • Version 1.1: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description