6IC2

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

PDB DOI: https://doi.org/10.2210/pdb6IC2/pdb

Classification: LIGASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2018-12-01 Released: 2019-05-15
Deposition Author(s): Angeli, A., Ferraroni, M., Supuran, C.T., Carta, F.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.15 Å
R-Value Free: 0.268
R-Value Work: 0.243
R-Value Observed: 0.244

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

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

PubMed: 31038135 Search on PubMed
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.

Macromolecule Content

Total Structure Weight: 29.79 kDa
Atom Count: 2,335
Modelled Residue Count: 258
Deposited Residue Count: 260
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Carbonic anhydrase 2	A	260	Homo sapiens	Mutation(s): 0 Gene Names: CA2 EC: 4.2.1.1
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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P00918
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
BBJ Query on BBJ Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A]	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		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]