3m2w

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3m2w, resolution 2.41Å ()
Ligands: ,
Gene: MAPKAPK2 (Homo sapiens)
Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Related: 3kga


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

Crystal structure of MAPKAK kinase 2 (MK2) complexed with a spiroazetidine-tetracyclic ATP site inhibitor

Publication Abstract from PubMed

Spirocyclopropane- and spiroazetidine-substituted tetracycles 13D-E and 16A are described as orally active MK2 inhibitors. The spiroazetidine derivatives are potent MK2 inhibitors with IC(50)<3 nM and inhibit the release of TNFalpha (IC(50)<0.3 microM) from hPBMCs and hsp27 phosphorylation in anisomycin stimulated THP-1 cells. The spirocyclopropane analogues are less potent against MK2 (IC(50)=0.05-0.23 microM), less potent in cells (IC(50)<1.1 microM), but show good oral absorption. Compound 13E (100mg/kg po; bid) showed oral activity in rAIA and mCIA, with significant reduction of swelling and histological score.

In vivo and in vitro SAR of tetracyclic MAPKAP-K2 (MK2) inhibitors. Part II., Revesz L, Schlapbach A, Aichholz R, Dawson J, Feifel R, Hawtin S, Littlewood-Evans A, Koch G, Kroemer M, Mobitz H, Scheufler C, Velcicky J, Huppertz C, Bioorg Med Chem Lett. 2010 Aug 1;20(15):4719-23. Epub 2010 Apr 11. PMID:20591669

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

About this Structure

3m2w is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Revesz L, Schlapbach A, Aichholz R, Dawson J, Feifel R, Hawtin S, Littlewood-Evans A, Koch G, Kroemer M, Mobitz H, Scheufler C, Velcicky J, Huppertz C. In vivo and in vitro SAR of tetracyclic MAPKAP-K2 (MK2) inhibitors. Part II. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4719-23. Epub 2010 Apr 11. PMID:20591669 doi:10.1016/j.bmcl.2010.04.023

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