Uses
Cyclin-dependent kinases (CDKs) play a key role in regulating cell division by phosphorylating distinct substrates in different phases of the cell cycle. Cell cycle deregulation in many cancers often results from altered CDK activity. Thus, CDKs are potential pharmacological targets for anticancer agents. NU 6102 is a potent inhibitor of Cdk1 and Cdk2 with Ki values of 9 and 6 nM and IC50 values of 9.5 and 5.4 nM, respectively. NU 6102 inhibits Cdk4 activity with an IC50 value of 1.6 μM, suggesting it is most selective for Cdk2. Time-lapse videomicroscopy reveals that 20 μM NU 6102 delays cell entry into mitosis where most cells appear to eventually complete mitotic division but cannot correctly undergo cytokinesis, and hence become binucleated with an abnormal number of centrosomes. In SKUT-1B cancer cells a 24 h exposure to NU 6102 induced G2 arrest, inhibition of target protein phosphorylation, and cytotoxicity with an LC50 value of 2.6 μM.
Uses
NU6102 is a known potent inhibitor of CDK1, CDK2 and CDK7. Cyclin-dependent kinases play a key role in the regulation of cell division which is controlled by the phosphorylation of distinct substrates in different phases of the cell cycle. In any circumstance where the cell cycle is deregulated, cyclin-dependent kinases activities are altered. Since NU6102 is known to exert inhibitory activities against CDKs, it has potential to act as a control in the cell cycle, especially in various cancers. NU6102 is known to be an anticancer agent use to repress the expression of breast cancer cells.
Biological Activity
Cell permeable: yes', 'Primary Target
Cdk1/cyclin B, Cdk2/cyclin A3', 'Product competes with ATP.', 'Reversible: no', 'Target IC50: 9.5 nM, 5.4 nM against Cdk1/cyclin B, Cdk2/cyclin A3, respectively
in vivo
The pharmacokinetics of NU6102 is determined following i.v. and i.p. administration in Balb/C mice. The limited solubility of NU6102 meant the maximum administrable dose is 1 mg/kg i.v. and 10 mg/kg i.p. NU6102 is liberated following either i.p. or i.v. administration of NU6301, and following i.v. administration peak plasma levels of 12 μM NU6102 is observed 5 min post administration, whereas following administration of the maximum administrable dose of NU6102 i.v. the peak concentration achieved is 0.92 μM. The plasma half-life of NU6102 liberated following administration of NU6301 is 42 min following i.p. and 10 min following i.v. administration[3].
IC 50
Cdk1/cyclin B: 9.5 nM (IC
50); CDK2/cyclin A3: 5.4 nM (IC
50); CDK4: 1.6 μM (IC
50); DYRK1A: 0.9 μM (IC
50); PDK1: 0.8 μM (IC
50)
