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The discovery of carboline analogs as potent MAPKAP-K2 inhibitors.
Wu JP,
Wang J,
Abeywardane A,
Andersen D,
Emmanuel M,
Gautschi E,
Goldberg DR,
Kashem MA,
Lukas S,
Mao W,
Martin L,
Morwick T,
Moss N,
Pargellis C,
Patel UR,
Patnaude L,
Peet GW,
Skow D,
Snow RJ,
Ward Y,
Werneburg B,
White A.
Research and Development, Boehringer-Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA. jwu@rdg.boehringer-ingelheim.com
The discovery of a series of potent, carboline-based MK2 inhibitors is described. These compounds inhibit MK2 with IC50s as low as 10 nM, as measured in a DELFIA assay. An X-ray crystal structure reveals that they bind in a region near the p-loop and the hinge region of MK2a.
PMID: 17576063 [PubMed - indexed for MEDLINE]
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Cited by 1 PubMed Central article
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Rational mutagenesis to support structure-based drug design: MAPKAP kinase 2 as a case study.
Argiriadi MA, Sousa S, Banach D, Marcotte D, Xiang T, Tomlinson MJ, Demers M, Harris C, Kwak S, Hardman J, et al.
BMC Struct Biol. 2009 Mar 18; 9:16. Epub 2009 Mar 18.
[BMC Struct Biol. 2009]
Structures reported by this article