4uy1

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Novel pyrazole series of group X Secretory Phospholipase A2 (sPLA2-X) inhibitors

Structural highlights

4uy1 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:1PE, CA, DMS, PEG, TJM
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PA2GX_HUMAN PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Has a powerful potency for releasing arachidonic acid from cell membrane phospholipids. Prefers phosphatidylethanolamine and phosphatidylcholine liposomes to those of phosphatidylserine.

Publication Abstract from PubMed

The discovery of potent novel pyrazole containing group X secreted phospholipase A2 inhibitors via structure based virtual screening is reported. Docking was applied on a large set of in-house fragment collection and pharmacophore feature matching was used to filter docking poses. The selected virtual screening hits was run in NMR screening, a potent pyrazole containing fragment hit was identified and confirmed by its complex X-ray structure and the following biochemical assay result. Expansion on the fragment hit has led to further improvement of potency while maintaining high ligand efficiency, thus supporting the further development of this chemical series.

Discovery of a novel pyrazole series of group X secreted phospholipase A2 inhibitor (sPLAX) via fragment based virtual screening.,Chen H, Knerr L, Kerud T, Hallberg K, Oster L, Rohman M, Osterlund K, Beisel HG, Olsson T, Brengdhal J, Sandmark J, Bodin C Bioorg Med Chem Lett. 2014 Sep 30. pii: S0960-894X(14)01011-7. doi:, 10.1016/j.bmcl.2014.09.058. PMID:25316315[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
2 reviews cite this structure
pCRP-mCRP Dissociation Mechanisms as Potential Targets for the Development of Small-Molecule Anti-Inflammatory Chemotherapeutics.
Caprio et al. (2018)
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2 other articles
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See Also

References

  1. ↑ Chen H, Knerr L, Kerud T, Hallberg K, Oster L, Rohman M, Osterlund K, Beisel HG, Olsson T, Brengdhal J, Sandmark J, Bodin C. Discovery of a novel pyrazole series of group X secreted phospholipase A2 inhibitor (sPLAX) via fragment based virtual screening. Bioorg Med Chem Lett. 2014 Sep 30. pii: S0960-894X(14)01011-7. doi:, 10.1016/j.bmcl.2014.09.058. PMID:25316315 doi:http://dx.doi.org/10.1016/j.bmcl.2014.09.058

Contents


PDB ID 4uy1

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