| Kinase Assay: |
| Proc Natl Acad Sci U S A,2001 Nov 20;98(24):13681-6. | | SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase.[Pubmed: 11717429] | Jun N-terminal kinase (JNK) is a stress-activated protein kinase that can be induced by inflammatory cytokines, bacterial endotoxin, osmotic shock, UV radiation, and hypoxia.
METHODS AND RESULTS:
We report the identification of an anthrapyrazolone series with significant inhibition of JNK1, -2, and -3 (K(i) = 0.19 microM). SP600125 is a reversible ATP-competitive inhibitor with >20-fold selectivity vs. a range of kinases and enzymes tested. In cells, SP600125 dose dependently inhibited the phosphorylation of c-Jun, the expression of inflammatory genes COX-2, IL-2, IFN-gamma, TNF-alpha, and prevented the activation and differentiation of primary human CD4 cell cultures. In animal studies, SP600125 blocked (bacterial) lipopolysaccharide-induced expression of tumor necrosis factor-alpha and inhibited anti-CD3-induced apoptosis of CD4(+) CD8(+) thymocytes.
CONCLUSIONS:
Our study supports targeting JNK as an important strategy in inflammatory disease, apoptotic cell death, and cancer. |
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| Cell Research: |
| Cancer Res, 2010, 70(24),10255-64. | | Targeting the mitotic checkpoint for cancer therapy with NMS-P715, an inhibitor of MPS1 kinase.[Pubmed: 21159646] | Cell lines: HCT116, A2780, and U2OS cells
Concentrations: 0–5 μM, dissolved in 0.1% DMSO
Incubation Time: 72 hours
Method:
Cells are seeded in 384 well-plates. One day after seeding, the cells are treated with SP600125 for 72 hours and the plates are then processed using a CellTiter-Glo assay. Inhibitory activity is evaluated comparing treated versus control data and IC50 value of proliferation is calculated.
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