4PV0: Crystal Structure Of Spleen Tyrosine Kinase (syk) In Complex With An Imidazopyrazine Inhibitor

Citation:
Abstract
Spleen tyrosine kinase (Syk) is an attractive drug target in autoimmune, inflammatory, and oncology disease indications. The most advanced Syk inhibitor, R406, 1 (or its prodrug form fostamatinib, 2), has shown efficacy in multiple therapeutic indications, but its clinical progress has been hampered by dose-limiting adverse effects that have been attributed, at least in part, to the off-target activities of 1. It is expected that a more selective Syk inhibitor would provide a greater therapeutic window. Herein we report the discovery and optimization of a novel series of imidazo[1,2-a]pyrazine Syk inhibitors. This work culminated in the identification of GS-9973, 68, a highly selective and orally efficacious Syk inhibitor which is currently undergoing clinical evaluation for autoimmune and oncology indications.
PDB ID: 4PV0Download
MMDB ID: 120143
PDB Deposition Date: 2014/3/14
Updated in MMDB: 2014/05
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 4PV0: monomeric; determined by author and by software (PISA)
Molecular Components in 4PV0
Label Count Molecule
Protein (1 molecule)
1
Tyrosine-protein Kinase SYK(Gene symbol: SYK)
Molecule annotation
Chemicals (6 molecules)
1
1
2
5
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.