GDC-0425 hydrochloride
GDC-0425 hydrochloride (RG-7602 hydrochloride) is an orally active, highly selective ChK1 inhibitor. GDC-0425 hydrochloride abrogates cell cycle arrest and inhibits genomic repair. GDC-0425 hydrochloride potently suppresses Gemcitabine (HY-17026)-induced pCDK1/2 expression. GDC-0425 hydrochloride can be used in research related to osteosarcoma, ovarian cancer, basal (triple-negative) breast cancer, and colorectal cancer.
For research use only. We do not sell to patients.
- CAS No.: 1778671-05-8
- Formula: C18H21Cl2N5O
- Molecular Weight:394.30
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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Chk1 |
CDK2 |
CDK1 |
GDC-0425 (3 μM; 48 h) hydrochloride alters the cell cycle distribution of both sensitive and resistant cancer cell lines, but induces the formation of apoptotic sub-G0/G1 cell populations only in sensitive osteosarcoma, ovarian cancer and breast cancer cell lines[3].
GDC-0425 (3 μM; 24 h) hydrochloride induces hyperphosphorylation of Chk1 in U-2 OS cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:cancer cell lines (143B PML BK TK, COV413B, HCC70, SW1353, OVISE, HCC1419)
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Concentration:3 μM
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Incubation Time:48 h
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Result:Reduced the S phase population and increased the G0/G1 phase population in both sensitive and resistant cell lines (except SW1353).
Caused a large increase in the sub-G0/G1 population (apoptotic cells) only in sensitive cell lines.
GDC-0425 (75 mg/kg; p.o.; 3 times per week; 15 days) alone partially suppresses osteosarcoma tumor growth, while combination with gemcitabine induces significant tumor regression with good tolerability in NCr nude mice[3].
GDC-0425 (50-75 mg/kg; p.o.; 3 times per week) alone partially suppresses triple-negative breast cancer (HCC1806) tumor growth, while combinations with gemcitabine induce significant tumor regression with good tolerability in NCr nude mice[3].
GDC-0425 (50-75 mg/kg; p.o.; 3 times per week) alone partially suppresses triple-negative breast cancer (HCC70) tumor growth, while combinations with gemcitabine induce significant tumor regression in NCr nude mice[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NCR nude (female; subcutaneous xenograft of TP53 mutant HT-29 colorectal cancer cells, tumors grown to 300-450 mm3)[2]
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Dosage:50 mg/kg
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Administration:p.o.; single dose; administered 16 hours after gemcitabine
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Result:Caused marked inhibition of gemcitabine-induced pCDK1/2 expression.
Showed little effect on pCDK1/2 expression when administered alone.
Left Ki-67 expression in surviving tumor cells relatively consistent across treatment groups.
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Animal Model:NCr nude mice[3]
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Dosage:75 mg/kg (single-agent); 75 mg/kg (in combination with gemcitabine 120 mg/kg)
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Administration:p.o.; 3 times per week; i.p. (weekly, gemcitabine)
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Result:Caused partial suppression of tumor growth (single-agent).
Induced significant tumor regression, with tumor volumes remaining near baseline over the 15-day treatment period (in combination with gemcitabine).
Did not cause significant body weight loss (in combination with gemcitabine).
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Animal Model:NCr nude mice[3]
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Dosage:50 mg/kg (single-agent); 75 mg/kg (single-agent); 50 mg/kg (in combination with gemcitabine 120 mg/kg); 75 mg/kg (in combination with gemcitabine 120 mg/kg)
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Administration:p.o.; 3 times per week; i.p. (weekly, gemcitabine)
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Result:Caused partial suppression of tumor growth at 50 mg/kg and 75 mg/kg (single-agent).
Induced significant tumor regression, with tumor volumes remaining near baseline over the treatment period (in combination with gemcitabine at both doses).
Did not cause significant body weight loss (in combination with gemcitabine).\nCaused partial suppression of tumor growth at 50 mg/kg and 75 mg/kg (single-agent).
Induced significant tumor regression, with tumor volumes remaining near baseline over the treatment period (in combination with gemcitabine at both doses).
Chemical Information
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CAS No. 1778671-05-8
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Molecular Weight 394.30
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Formula C18H21Cl2N5O
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SMILES
N#CC1=NC=C2NC3=C(C2=C1OC4CCN(CC4)CC)C=CC=N3.Cl.Cl
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Synonyms
RG-7602 hydrochloride
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
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. [Content Brief]
[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. [Content Brief]
[3]. Lee HJ, Cao Y, Pham V, et al.. Ras-MEK Signaling Mediates a Critical Chk1-Dependent DNA Damage Response in Cancer Cells. Molecular cancer therapeutics. 2017 Apr;16(4):694-704. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GDC-0425 hydrochloride Related Classifications
HY-19926A Related Classifications
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