ChemicalBook CAS DataBase List 1200129-48-1

1200129-48-1

Name	GDC-0425
CAS	1200129-48-1
Molecular Formula	C18H19N5O
MDL Number	MFCD31536987
Molecular Weight	321.38
MOL File	1200129-48-1.mol

Chemical Properties

Boiling point	589.2±50.0 °C(Predicted)
density	1.33±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
form	Solid
pka	10.73±0.50(Predicted)
color	Off-white to brown
Water Solubility	Water : 25 mg/mL (77.79 mM; ultrasonic and adjust pH to 3 with HCl)

Hazard Information

Uses

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].

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].

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.

IC 50

Chk1

storage

Store at -20°C

References

[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. DOI:10.1002/bmc.3775
[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. DOI:10.1158/1078-0432.CCR-16-1782
[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. DOI:10.1158/1535-7163.MCT-16-0504

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