3QTF

Design and SAR of macrocyclic Hsp90 inhibitors with increased metabolic stability and potent cell-proliferation activity


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.57 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.188 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Design and SAR of macrocyclic Hsp90 inhibitors with increased metabolic stability and potent cell-proliferation activity.

Zapf, C.W.Bloom, J.D.McBean, J.L.Dushin, R.G.Nittoli, T.Ingalls, C.Sutherland, A.G.Sonye, J.P.Eid, C.N.Golas, J.Liu, H.Boschelli, F.Hu, Y.Vogan, E.Levin, J.I.

(2011) Bioorg Med Chem Lett 21: 2278-2282

  • DOI: https://doi.org/10.1016/j.bmcl.2011.02.101
  • Primary Citation of Related Structures:  
    3QTF

  • PubMed Abstract: 

    A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. A basic nitrogen within the tether linking the aniline nitrogen atom to a tetrahydroindolone moiety allowed access to compounds with good physical properties. Important structure-activity relationship information was obtained from this series which led to the discovery of a soluble and stable compound which is potent in an Hsp90 binding and cell-proliferation assay.


  • Organizational Affiliation

    Medicinal Chemistry, Pfizer, 401 N. Middletown Road, Pearl River, NY 10965, USA. christoph.zapf@pfizer.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Heat shock protein HSP 90-alpha226Homo sapiensMutation(s): 0 
Gene Names: HSP90AHSP90AA1HSPC1HSPCA
UniProt & NIH Common Fund Data Resources
Find proteins for P07900 (Homo sapiens)
Explore P07900 
Go to UniProtKB:  P07900
PHAROS:  P07900
GTEx:  ENSG00000080824 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07900
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
05S
Query on 05S

Download Ideal Coordinates CCD File 
B [auth A](6S)-6,15,15,18-tetramethyl-17-oxo-2,3,4,5,6,7,14,15,16,17-decahydro-1H-8,12-(metheno)[1,4,9]triazacyclotetradecino[9,8-a]indole-9-carboxamide
C24 H32 N4 O2
DGOVAFNEOBXFEF-AWEZNQCLSA-N
DMS
Query on DMS

Download Ideal Coordinates CCD File 
C [auth A]DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
05S Binding MOAD:  3QTF IC50: 110 (nM) from 1 assay(s)
BindingDB:  3QTF IC50: 110 (nM) from 1 assay(s)
PDBBind:  3QTF IC50: 110 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.57 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.188 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.264α = 90
b = 90.718β = 90
c = 98.379γ = 90
Software Package:
Software NamePurpose
StructureStudiodata collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-06
    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