[CAS NO. 1200129-48-1] GDC-0425
PRODUCTS SPECIFICATIONS [1200129-48-1]
DESCRIPTION [1200129-48-1]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 321.38 |
| Molecular Formula | C18H19N5O |
| SMILES | N#CC1=NC=C2C(C3=CC=CN=C3N2)=C1OC4CCN(CC)CC4 |
Summary
IC50 & Target
|
Chk1 |
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]
.
MCE 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. |
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] .
MCE 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. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT01359696 | Genentech, Inc. |
Solid Tumor
|
July 11, 2011 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
H 2 O : 25 mg/mL ( 77.79 mM ; ultrasonic and adjust pH to 3 with HCl)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.1116 mL | 15.5579 mL | 31.1158 mL |
| 5 mM | 0.6223 mL | 3.1116 mL | 6.2232 mL |
| 10 mM | 0.3112 mL | 1.5558 mL | 3.1116 mL |
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.
- [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.