1200129-48-1

1200129-48-1 structure

Name: GDC-0425
Chemical Name: 5-[(1-Ethyl-4-piperidinyl)oxy]-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine-6-carbonitrile
CAS Number: 1200129-48-1
Molecular Formula: C₁₈H₁₉N₅O
Molecular Weight: 321.38
Catalog: Signaling Pathways Cell Cycle/DNA Damage Checkpoint Kinase (Chk)
Create Date: 2018-06-12 10:17:40
Modify Date: 2024-01-14 17:48:32
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].

Name	5-[(1-Ethyl-4-piperidinyl)oxy]-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine-6-carbonitrile
Synonyms	5-[(1-Ethyl-4-piperidinyl)oxy]-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine-6-carbonitrile 9H-Pyrrolo[2,3-b:5,4-c']dipyridine-6-carbonitrile, 5-[(1-ethyl-4-piperidinyl)oxy]-

Description	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].
Related Catalog	Research Areas >> Cancer Signaling Pathways >> Cell Cycle/DNA Damage >> Checkpoint Kinase (Chk)
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]. 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]. 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.
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.

Density	1.3±0.1 g/cm3
Boiling Point	589.2±50.0 °C at 760 mmHg
Molecular Formula	C₁₈H₁₉N₅O
Molecular Weight	321.38
Flash Point	310.2±30.1 °C
Exact Mass	321.158966
LogP	3.82
Vapour Pressure	0.0±1.7 mmHg at 25°C
Index of Refraction	1.686

1200129-48-1	1434048-34-6
2238822-07-4	1637394-01-4
1001264-89-6	2252277-73-7
1382979-44-3	2377352-49-1
957054-30-7	1133432-50-4
2415469-53-1	2415561-98-5
2415552-57-5	2415624-51-8
2415632-20-9	2415631-03-5
2415512-10-4	2415534-55-1
2415471-49-5	2415523-46-3