Wee1 is a tyrosine kinase belonging to the Ser/Thr family of protein kinases. Wee1 catalyzes the inhibitory tyrosine phosphorylation of CDC2/cyclin B kinase, and appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from cytoplasmically activated CDC2 kinase. In details, wee1 acts as a negative regulator of mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating phosphorylation of CDK1 on Tyr-15[3].
PD0166285 is a wee1 inhibitor. Data obtained by a wee1 mass screening revealed that the inhibitory IC50 of PD0166285 against wee1 was 24 nM[2]. PD0166285 also inhibited myt1 kinase, a dual-specificity protein kinase that phosphorylates Cdc2 on both Thr 14 and Tyr 15[4] with an IC50 of 72 nM[2]. 0.5μM PD0166285 dramatically inhibited irradiation-induced Cdc2 phosphorylation at the Tyr-15 and Thr-14 in the cancer cell lines of hct116, HT29, DLD-1, hct8, H460, Hela and C26[2]. In a cell cycle assay, G2 arrest in HT29 cells were induced by irradiation as evidenced by the increase of G2-M population to 66-69%. 4h treatment of PD0166285 at the concentration of 0.25 μM decreased the G2-M cell population to 37%[2]. According to another report, 4h treatment of 0.5 μM PD0166285 resulted in decrease of cyclin D mRNA to 42.1% of baseline level as revealed by real-time PCR in B16 cells[1].
In an E98 orthotopic tumor model established by intracranial injection of tumor cells into Balb/c nude mice, PD0166285 was administrated daily at the concentration of 20 μM via i.p. injection for 5 days. The results was that PD0166285 improved survival of tumor bearing mice[5].
PD0166285 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
C6 cell
Function assay
Inhibition of C6 cell proliferation in sulforhodamine B assay, IC50=0.34 μM
9703473
C6 cells
Function assay
Inhibition of PDGF-induced autophosphorylation of PDGF-R in C6 cells, IC50=5 nM
9703473
HCT-8
Function assay
Inhibitory activity against HCT-8 human colon adenocarcinoma cells was determined, IC50=0.42 μM
10956222
HEK293 cells
Function assay
Binding affinity to human full-length His-tagged Myt1 kinase expressed in HEK293 cells by TR-FRET based binding assay, IC50=7.2 nM
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