Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
