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Pyrrolopyridine Inhibitors of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK-2)
Open accessAbstract
A new class of potent kinase inhibitors selective for mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK-2) for the treatment of rheumatoid arthritis has been prepared and evaluated. These inhibitors have IC50 values as low as 10 nM against the target and have good selectivity profiles against a number of kinases including CDK2, ERK, JNK, and p38. These MK-2 inhibitors have been shown to suppress TNFalpha production in U397 cells and to be efficacious in an acute inflammation model. The structure-activity relationships of this series, the selectivity for MK-2 and their activity in both in vitro and in vivo models are discussed. The observed selectivity is discussed with the aid of an MK-2/inhibitor crystal structure.
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Citations
Cites
MAPKAP kinases — MKs — two's company, three's a crowd
Gaestel, M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1834 · Cited by 413
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Proteasome activation by small molecules
Leestemaker, Y., de Jong, A., Witting, K. F., Penning, R., Schuurman, K., Rodenko, B., Zaal, E. A., van de Kooij, B., Laufer, S., Heck, A. J. R., et al. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.05.010 · Cited by 144
Metadata
- Authors
- Anderson, D. R., Meyers, M. J., Vernier, W. F., Mahoney, M. W., Kurumbail, R. G., Caspers, N., Poda, G. I., Schindler, J. F., Reitz, D. B., & Mourey, R. J.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2007-05-01
- Volume
- 50
- Issue
- 11
- Pages
- 2647-2654
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2091448951
- Cited by
- 170
- References
- 1
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- green
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