Kenpaullone 是一种CDK1/cyclin B和GSK-3β抑制剂，IC50值分别为 0.4 μM 和 23 nM。它也抑制 CDK2/cyclin A、CDK2/cyclin E 和 CDK5/p25 的活性，IC50值分别为 0.68 μM、7.5 μM 和 0.85 μM。。它通过增强 TGFβ-Smad3 信号通路增加和延长 foxp3 基因的转录来促进 iTreg 细胞分化。

Kenpaullone, a potent CDK1, CDK2 and CDK5 inhibitor, as new enhancer for iTreg cell differentiation. Kenpaullone promotes iTreg cell differentiation through increased and prolonged transcription of foxp3 gene by enhancing TGFβ-Smad3 signaling pathway.

In HEK-293 cells, phosphorylation of the endogenous GSK3α on Tyr279 is greatly decreased after prolonged incubation with Kenpaullone. Also, the Phosphorylation of the endogenous GSK3β also decreases, although less markedly. Kenpaullone also induces the dephosphorylation of both GSK3 isoforms in SH-SY5Y cells and PC12 cells. Kenpaullone (20 μM) strongly suppresses the autophosphorylation of GSK3β at Tyr216 in vitro whether GSK3 is expressed in Sf21 cells or in E. coli[2][3].

IC50 determination: Active GST-LRRK2 (1326-2527), GST-LRRK2 [G2019S] (1326-2527), GST-LRRK2 [A2016T] (1326-2527) and GST-LRRK2 [A2016T+G2019S] (1326-2527) enzyme is purified with glutathione sepharose from HEK293 cell lysate 36 h following transient transfection of the appropriate cDNA constructs. Peptide kinase assays, performed in duplicate, are set up in a total volume of 40 μL containing 0.5 μg LRRK2 kinase (which at approximately 10% purity gives a final concentration of 8 nM) in 50 mM Tris/HCl, pH 7.5, 0.1 mM EGTA, 10 mM MgCl2, 20 μM Nictide, 0.1 μM [γ-32P]ATP (~500 cpm/pmol) and the indicated concentrations of inhibitor dissolved in DMSO. After incubation for 15 min at 30 °C, reactions are terminated by spotting 35 μL of the reaction mix onto P81 phosphocellulose paper and immersion in 50 mM phosphoric acid. Samples are washed extensively and the incorporation of [γ-32P]ATP into Nictide is quantified by Cerenkov counting. IC50 values are calculated with GraphPad Prism using non-linear regression analysis.

142273-20-9

C16H11BrN2O

327.18

9-溴-7,12-二氢吲哚并[3,2-D][1]苯并氮杂卓-6(5H)-酮;NSC-664704;9-Bromopaullone

Ethanol:1.6 mg/mL (5 mM)),with gentle warming
DMSO:32.7 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years