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Category:Jewellery retailers of the United KingdomSelective inhibition of cyclin-dependent kinase 5 and 6 with inhibitors of the Cdc25 family of phosphatases.
The Cdc25 family of phosphatases is a regulator of cyclin-dependent kinases (CDKs) and is involved in the regulation of various cell functions. The major substrates of Cdc25 phosphatases are CDKs, and CDKs are also essential for their own dephosphorylation. This feature makes the Cdc25 family of phosphatases potential targets for therapeutic intervention. To explore the potential of Cdc25 phosphatases as anti-cancer targets, we used a human kinome array to select inhibitors with selective activity against Cdc25C and Cdc25B. We evaluated these inhibitors for their anti-proliferative effects in human cancer cell lines and for their selectivity in mice. Using a cell-based assay that measures Cdc25-regulated dephosphorylation of endogenous cyclin-dependent kinases, we found that several compounds selectively inhibited Cdc25C phosphatase activity. One of these compounds inhibited Cdc25C-dependent cell growth and mitosis in a panel of cell lines at concentrations that were non-toxic to normal cells. As expected from its effect on Cdc25C, it also inhibited CDK1 and CDK2, but not CDK4 and CDK6. When combined with roscovitine, an inhibitor of CDKs that also inhibits Cdc25 phosphatases, the compound partially reversed the roscovitine-induced inhibition of cell proliferation and mitosis. In mice, the compound was well tolerated at concentrations that were 20-40 times the human effective dose, and the compound decreased proliferation in tumors from two cell lines that were sensitive to roscovitine. These data support the development of Cdc25 phosphatase inhibitors as anticancer agents.Police chiefs have welcomed a promise by the Home Secretary to reform the government's arbitrary detaining power, but said the need to tackle "institutional racism" would not be met by her measures alone.
Sajid Javid, who was appointed Home Secretary by Theresa May in July, said the number of people being be359ba680
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