6IC2 | pdb_00006ic2

Polypharmacology of Epacadostat: a Potent and Selective Inhibitor of the Tumor Associated Carbonic Anhydrases IX and XII

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.15 Å
  • R-Value Free: 
    0.268 (Depositor), 0.270 (DCC) 
  • R-Value Work: 
    0.243 (Depositor), 0.240 (DCC) 
  • R-Value Observed: 
    0.244 (Depositor) 

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Ligand Structure Quality Assessment 

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Literature

Polypharmacology of epacadostat: a potent and selective inhibitor of the tumor associated carbonic anhydrases IX and XII.

Angeli, A., Ferraroni, M., Nocentini, A., Selleri, S., Gratteri, P., Supuran, C.T., Carta, F.

(2019) Chem Commun (Camb) 55: 5720-5723

  • DOI: https://doi.org/10.1039/c8cc09568j
  • Primary Citation of Related Structures:  
    6IC2

  • PubMed Abstract: 

    Epacadostat (EPA), a selective indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, has been investigated in vitro as a human (h) Carbonic Anhydrase Inhibitor (CAI). The kinetic data clearly show, for the first time, EPA to be a highly effective and selective inhibitor for the tumor-associated isoforms hCA IX/XII. We report the high resolution X-ray crystal structure of the EPA-hCA II adduct, and assessed its binding mode to CA IX/XII by means of computational techniques. EPA may exert antitumor effects also due to the potent inhibition of the tumor-associated CAs.

    • Organizational Affiliation: 

    University of Florence, NEUROFARBA Dept., Sezione di Farmaceutica e Nutraceutica, Via Ugo Schiff 6, Sesto Fiorentino, 50019, Florence, Italy. claudiu.supuran@unifi.it fabrizio.carta@unifi.it.


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2260Homo sapiensMutation(s): 0 
Gene Names: CA2
EC: 4.2.1.1 (PDB Primary Data), 4.2.1.69 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P00918 (Homo sapiens)
Explore P00918 
Go to UniProtKB:  P00918
PHAROS:  P00918
GTEx:  ENSG00000104267 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00918
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BBJ
Query on BBJ
Download Ideal Coordinates CCD File 
C [auth A]N-(3-bromo-4-fluorophenyl)-N'-hydroxy-4-{[2-(sulfamoylamino)ethyl]amino}-1,2,5-oxadiazole-3-carboximidamide
C11 H13 Br F N7 O4 S
FBKMWOJEPMPVTQ-UHFFFAOYSA-N
ZN
Query on ZN
Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.15 Å
  • R-Value Free:  0.268 (Depositor), 0.270 (DCC) 
  • R-Value Work:  0.243 (Depositor), 0.240 (DCC) 
  • R-Value Observed: 0.244 (Depositor) 
Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.418α = 90
b = 41.385β = 104.54
c = 72.32γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
REFMACphasing

Structure Validation

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Ligand Structure Quality Assessment 

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View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-05-15
    Type: Initial release
  • Version 1.1: 2019-05-22
    Changes: Data collection, Database references
  • Version 1.2: 2024-05-15
    Changes: Advisory, Data collection, Database references