GDC-0425 (RG-7602) is an orally available, highly selective small molecule ChK1 inhibitor. GDC-0425 can be used for the research of various malignancies[1][2].
IC50 & Target[1]
Chk1
体外研究 (In Vitro)
MEK inhibition either by pharmacologic inhibitors or RNAi-mediated gene silencing significantly protected cells from reduced viability upon GDC-0425 treatment[3]. GDC-0425 (3 μM; 24 hours) treatment results the hyperphosphorylation of Chk1[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[3]
Cell Line:
Chk1-positive breast cancer cell lines
Concentration:
0.001, 0.01, 0.1, 1, 10 mM
Incubation Time:
72 hours
Result:
Reduced cell proliferation.
Cell Viability Assay[3]
Cell Line:
U-2 OS cells
Concentration:
3 μM
Incubation Time:
24 hours
Result:
Led to hyperphosphorylation of Chk1.
体内研究 (In Vivo)
GDC-0425 exhibits partial suppression of tumor growth. The Gemcitabine/GDC-0425 combination results in significant tumor regression in all tested models[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
NCr nude mice bearing xenografts of both osteosarcoma and triple-negative breast cancer models (143B PML BK TK, HCC1806, and HCC70 cell lines)[3]
Dosage:
For the 4-arm study, mice were treated with vehicle, Gemcitabine 120 mg/kg, GDC-0425 75 mg/kg alone, or Gemcitabine and GDC-0425 combination for 15 days. For 6-arm studies of HCC1806 and HCC70 models, mice were treated with vehicle, Gemcitabine 120 mg/kg, GDC-0425 50 mg/kg, GDC-0425 75 mg/kg alone, or Gemcitabine and GDC-0425 combination.
Administration:
Orally administrated at 24, 48, and 72 hours after gemcitabine administration by intraperitoneal injection.
Result:
Exhibited partial suppression of tumor growth upon treatment with either Gemcitabine or GDC-0425 alone. Notably, the Gemcitabine/GDC-0425 combination resulted in significant tumor regression in all tested models.
分子量
321.38
Formula
C18H19N5O
CAS 号
1200129-48-1
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
H2O : 25 mg/mL (77.79 mM; ultrasonic and adjust pH to 3 with HCl)
[1]. Xiao Ding, et al. A supported liquid extraction LC-MS/MS method for determination of concentrations of GDC-0425, a small molecule Checkpoint kinase 1 inhibitor, in human plasma. Biomed Chromatogr. 2016 Dec;30(12):1984-1991.
[2]. Jeffrey R Infante, et al. Phase I Study of GDC-0425, a Checkpoint Kinase 1 Inhibitor, in Combination with Gemcitabine in Patients with Refractory Solid Tumors. Clin Cancer Res. 2017 May 15;23(10):2423-2432.
[3]. Ho-June Lee, et al. Ras-MEK Signaling Mediates a Critical Chk1-Dependent DNA Damage Response in Cancer Cells. Mol Cancer Ther. 2017 Apr;16(4):694-704.
