3VW6

Crystal structure of human apoptosis signal-regulating kinase 1 (ASK1) with imidazopyridine inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Design and biological evaluation of imidazo[1,2-a]pyridines as novel and potent ASK1 inhibitors.

Terao, Y.Suzuki, H.Yoshikawa, M.Yashiro, H.Takekawa, S.Fujitani, Y.Okada, K.Inoue, Y.Yamamoto, Y.Nakagawa, H.Yao, S.Kawamoto, T.Uchikawa, O.

(2012) Bioorg Med Chem Lett 22: 7326-7329

  • DOI: https://doi.org/10.1016/j.bmcl.2012.10.084
  • Primary Citation of Related Structures:  
    3VW6

  • PubMed Abstract: 

    Imidazo[1,2-a]pyridine derivatives were designed, synthesized, and evaluated as inhibitors of the apoptosis signal-regulating kinase 1 (ASK1). These were based on a benzothiazole derivative that was discovered from high-throughput screening of our compound library. As a result, we identified potent, selective, and orally bioavailable ASK1 inhibitors for wide range of therapeutic targets.


  • Organizational Affiliation

    Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa 251-8555, Japan. yoshito.terao@takeda.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mitogen-activated protein kinase kinase kinase 5
A, B
269Homo sapiensMutation(s): 0 
Gene Names: MAP3K5ASK1MAPKKK5MEKK5
EC: 2.7.11.25
UniProt & NIH Common Fund Data Resources
Find proteins for Q99683 (Homo sapiens)
Explore Q99683 
Go to UniProtKB:  Q99683
PHAROS:  Q99683
GTEx:  ENSG00000197442 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ99683
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
IM6
Query on IM6

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
4-tert-butyl-N-[6-(1H-imidazol-1-yl)imidazo[1,2-a]pyridin-2-yl]benzamide
C21 H21 N5 O
SMJAMOAYGIVKRI-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
IM6 BindingDB:  3VW6 IC50: 14 (nM) from 1 assay(s)
PDBBind:  3VW6 IC50: 14 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 78.032α = 90
b = 78.032β = 90
c = 425.295γ = 120
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2012-10-31
    Type: Initial release
  • Version 1.1: 2017-12-20
    Changes: Database references
  • Version 1.2: 2024-03-20
    Changes: Data collection, Database references, Derived calculations