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 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Calu1
0 nM, 200 nM, 400 nM, 800 nM
48 hours
PD0166285 significantly reduced the number and size of cell colonies and showed anti-tumor effects through CCK8 assay.
Cancer Cell Int. 2024 Sep 13;24(1):315.
NCI-H520
0 nM, 200 nM, 400 nM, 800 nM
48 hours
PD0166285 significantly reduced the number and size of cell colonies and showed anti-tumor effects through CCK8 assay.
Cancer Cell Int. 2024 Sep 13;24(1):315.
NCI-H226
0 nM, 200 nM, 400 nM, 800 nM
48 hours
PD0166285 significantly reduced the number and size of cell colonies and showed anti-tumor effects through CCK8 assay.
Cancer Cell Int. 2024 Sep 13;24(1):315.
HeLa cells
20 nM BTZ and 0.25 μM PD0166285
24 h
BP-Combo (combined BTZ and PD0166285 treatment) significantly increased the proportion of pyroptotic cells and LDH release.
Signal Transduct Target Ther. 2024 Jul 12;9(1):181.
Signal Transduct Target Ther. 2024 Jul 12;9(1):181.
Calu1
0 nM, 200 nM, 400 nM, 800 nM
48 hours
To evaluate the effect of PD0166285 on LUSC cell proliferation, results showed that PD0166285 significantly reduced the number and size of cell colonies.
Cancer Cell Int. 2024 Sep 13;24(1):315.
NCI-H520
0 nM, 200 nM, 400 nM, 800 nM
48 hours
To evaluate the effect of PD0166285 on LUSC cell proliferation, results showed that PD0166285 significantly reduced the number and size of cell colonies.
Cancer Cell Int. 2024 Sep 13;24(1):315.
NCI-H226
0 nM, 200 nM, 400 nM, 800 nM
48 hours
To evaluate the effect of PD0166285 on LUSC cell proliferation, results showed that PD0166285 significantly reduced the number and size of cell colonies.
Cancer Cell Int. 2024 Sep 13;24(1):315.
MCF10A cells
1 μM
PD0166285 shortens G2 phase and overcomes the cycloheximide-induced G2 arrest
Cell Rep. 2020 Jul 14;32(2):107901.
PD0166285 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
LUSC nude mouse model
Intraperitoneal injection
10 mg/kg
Tumor size was measured every 2 days for 2 weeks
Combination therapy of PD0166285 and cisplatin significantly inhibited tumor growth and increased apoptosis.
Cancer Cell Int. 2024 Sep 13;24(1):315.
C57BL/6J mice
Hepa1-6 subcutaneous xenograft model
Intraperitoneal injection
0.26 mg/kg
Every three days for five times
BP-Combo significantly suppressed tumor growth and metastasis, prolonged survival of tumor-bearing mice with no obvious toxicity.
Signal Transduct Target Ther. 2024 Jul 12;9(1):181.
Xenopus laevis embryos
Early embryonic cell cycles
Pretreated for 2-2.5 hours prior to fertilization and maintained at the same concentration after fertilization and jelly coat removal
50 μM
Single treatment, continued until the end of the first cell cycle
Investigate the effect of Wee1/Myt1 inhibition on embryonic cell cycle and viability. PD0166285 treatment significantly shortened the first cell cycle duration and dramatically reduced embryo viability.
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