The endogenous protein was sensitive to inhibitors and the purified protein. VRK2 VRK1 is sensitive to CDK inhibitors n Chstes we will further analyze the differential effect of inhibitors targeting proteins Like CDKs Cdk1 to proceed Inhibitor roscovitine and indirubin monoxime 39th Indirubin monoxime 39 had little effect was obtained in the concentration of 100 mM and not investigated further. VRK2 was more sensitive to the inhibitor of the activity and kinase VRK1 Cdk1 t was VRK2A fifty percent to 4 PF-04217903 mM inhibited in the presence of low ATP, Is similar to the Cdk1/cyclinB determined. It is important to note that the effect on both autophosphorylation and phosphorylation of H3 a pattern Similar follow shown in the diagrams. Roscovitine, a CDK inhibitor II pan breast cancer and lung cancer, inhibits the activity of t VRK2 of 50 percent to about 25 mM, which is h Ago than that reported for the inhibition and CDK1/cyclinB CDK2/cyclinA .
VRK1 is less sensitive to roscovitine and was not inhibited at concentrations much h Ago than 250 mM but there was a noticeable effect. In addition, a pan-inhibitor D Dusk, VX 680, in use in the clinical trials with no significant inhibitory effect on each VRK protein. Effect of PKC inhibitors, have RO 31 8220 and staurosporine on VRK1 and VRK2 Many inhibitors of PKC Proteinaktivit Reported OSU-03012 t. Among them, 31. RO 8220 and staurosporine, the Haupts Were chlich on protein kinase C, tested, and the apoptosis, inhibition of insulin secretion and block PDGF reaction among many other effects that require induce k Can PKC The effect of RO 31 8220 was tested in trials kinase VRK1 and VRK2A. Both kinases 50 percent inhibition was Similar 11-34 mM H3 phosphorylation or Autophosphorylierungsaktivit t, which is also significantly higher than the reported 27 for 5 nM PKC isoforms, although this is an inhibitor known to inhibit several kinases such as MSK1, S6K1 and RSK.
The effect on autophosphorylation and H3 phosphorylation followed a Hnlichen trend. In a large study found, appeared to be a potent inhibitor staurosporine, although not very efficient, VRK proteins. VRK1 is sensitive and 50 percent inhibition was at 15 mM staurosporine that much h Ago as the achieved IC50 of 3 nM for PKC. VRK2A was not inhibited by staurosporine. Therefore, staurosporine make the difference between VRK1 and VRK2 which is an unexpected observation since staurosporine is one of the least known specific inhibitors.
Effect of inhibitors targeting kinases DNA Sch the answer VRK2 VRK1 sensitive to AZD7762 cellular Ren answers to DNA Sch to include many different kinases, which may be suitable targets for drug development because they further educate cells to chemotherapeutic drugs important therapeutic. Several inhibitors targeting ATM, DNA PK and CHK1 / 2 were evaluated for their effect on the activity of t VRK2A VRK1 and tested. AZD7762 has only an inhibitor targeting both kinases CHK1 and CHK2 in answers serinethreonine DNA Sch To, which is currently used in clinical trials involved, t have some effect on the activity VRK had. Fifty percent inhibition of autophosphorylation and H3 phosphorylation VRK2A time was 30 mM. VRK1 was less sensitive than VRK2A, and some inhibition was detectable at 100 mM.