4U93 | pdb_00004u93

Crystal Structure of Hsp90-alpha N-domain Bound to the Inhibitor NVP-HSP990

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 
    0.213 (Depositor), 0.210 (DCC) 
  • R-Value Work: 
    0.185 (Depositor), 0.180 (DCC) 
  • R-Value Observed: 
    0.186 (Depositor) 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted 990Click on this verticalbar to view details

This is version 1.4 of the entry. See complete history. 


Literature

Design, Structure-Activity Relationship, and in Vivo Characterization of the Development Candidate NVP-HSP990.

McBride, C.M., Levine, B., Xia, Y., Bellamacina, C., Machajewski, T., Gao, Z., Renhowe, P., Antonios-McCrea, W., Barsanti, P., Brinner, K., Costales, A., Doughan, B., Lin, X., Louie, A., McKenna, M., Mendenhall, K., Poon, D., Rico, A., Wang, M., Williams, T.E., Abrams, T., Fong, S., Hendrickson, T., Lei, D., Lin, J., Menezes, D., Pryer, N., Taverna, P., Xu, Y., Zhou, Y., Shafer, C.M.

(2014) J Med Chem 57: 9124-9129

  • DOI: https://doi.org/10.1021/jm501107q
  • Primary Citation of Related Structures:  
    4U93, 4W7T

  • PubMed Abstract: 

    Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series which exhibited potent Hsp90 inhibition, good pharmacokinetics upon oral administration, and an excellent pharmacokinetic/pharmacodynamic relationship in vivo was developed from a commercial hit. The exploration of this series led to the selection of NVP-HSP990 as a development candidate.

    • Organizational Affiliation: 

    Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 5300 Chiron Way, Emeryville, California 94608, United States.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Heat shock protein HSP 90-alpha236Homo sapiensMutation(s): 0 
EC: 3.6.4.10
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 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
990
Query on 990
Download Ideal Coordinates CCD File 
B [auth A](7R)-2-amino-7-[4-fluoro-2-(6-methoxypyridin-2-yl)phenyl]-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one
C20 H18 F N5 O2
WSMQUUGTQYPVPD-OAHLLOKOSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
990 BindingDB:  4U93 IC50: 13 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free:  0.213 (Depositor), 0.210 (DCC) 
  • R-Value Work:  0.185 (Depositor), 0.180 (DCC) 
  • R-Value Observed: 0.186 (Depositor) 
Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 66.726α = 90
b = 99.237β = 90
c = 91.561γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PDB_EXTRACTdata extraction
MOLREPphasing
REFMACrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted 990Click on this verticalbar to view details

View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-11-19
    Type: Initial release
  • Version 1.1: 2014-11-26
    Changes: Database references
  • Version 1.2: 2016-07-20
    Changes: Data collection
  • Version 1.3: 2017-11-22
    Changes: Derived calculations, Refinement description
  • Version 1.4: 2023-12-27
    Changes: Data collection, Database references