GZD856
GZD856 formic is a potent and orally active PDGFRα/β inhibitor, with IC50s of 68.6 and 136.6 nM, respectively. GZD856 formic is also a Bcr-AblT315I inhibitor, with IC50s of 19.9 and 15.4 nM for native Bcr-Abl and the T315I mutant. GZD856 formic has antitumor activity.
For research use only. We do not sell to patients.
- CAS No.: 1257628-64-0
- Formula: C29H27F3N6O
- Molecular Weight:532.56
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
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PDGFRα 68.6 nM (IC50) |
PDGFRβ 136.6 nM (IC50) |
Bcr-AblT315I 15.4 nM (IC50) |
Bcr-Abl 19.9 nM (IC50) |
In Vitro
GZD856 (0.0032-10 μM, 72 h) exerts antiproliferative activity against a panel of lung cancer cells[1].
GZD856 (0.3-3 μM; 24-28 h) induces a dose-dependent G0/G1 phase arrest and apoptosis in H1703 but not A549 cells[1].
GZD856 (0.1-10 μM; 6 h) dose-dependently inhibits the PDGFRα/β phosphorylation and downstream signaling in H1703 and A549 cells[1].
GZD856 inhibits the proliferation of K562, K562R (Q252H) and murine Ba/F3 cells ectopically expressing Bcr-AblWT and Bcr-AblT315I, with IC50s of 2.2, 67.0, 0.64 and 10.8 nM, respectively[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:H1703, A549, Calu-6, 95-D, L-78, HCC827, SPCA-1, H1650, H1299, H522, H332 and H820 NSCLC cells
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Concentration:0.0032-10 μM
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Incubation Time:72 hours
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Result:Inhibited PDGFRα-overexpressing H1703 cells, with an IC50 of 0.25 μM.
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Cell Line:H1703 and A549 NSCLC cells
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Concentration:0.3, 1, 3 μM
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Incubation Time:24, 48 hours
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Result:Led to 54.1% apoptosis in H1703 cells at the concentration of 3.0 µM, whereas only 15.5% apoptotic A549 cells were observed under similar conditions.
Decreased the CDK4, cyclin D2, CDK2 and Cyclin E protein levels and activated of PARP and Caspase-3 cleavage in H1703 cells.
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Cell Line:H1703 and A549 NSCLC cells
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Concentration:0.1-10 μM
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Incubation Time:6 hours
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Result:Inhibited the phosphorylation of PDGFRα and PDGFRβ in a dose-dependent manner.
Observed the activation of downstream AKT, ERK1/2 and STAT3, with no obvious effects on total protein levels.
In Vivo
GZD856 (10 mg/kg; p.o. once daily for 8 d) potently inhibits tumor growth in mouse bearing xenograft K562 and Ba/F3 cells expressing Bcr-AblT315I[2].
GZD856 (5 mg/kg; a single i.v.) exhibits a long half-life (T1/2=19.97 h), optimal plasma exposure (Cmax=934.38 μg/L) and a AUC0-∞ (8165.8 μg/L h) in rats[1].
GZD856 (25 mg/kg; a single p.o.) exhibits a long half-life (T1/2=22.2 h), optimal plasma exposure (Cmax=899.5 μg/L) and a good oral bioavailability (BA=78%) in rats[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male CB17-SCID mice implanted with H1703 and A549 cancer cells[1]
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Dosage:10, 30 mg/kg
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Administration:Oral gavage once daily for 16 days
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Result:Displayed antitumor effects in H1703-xenograft mice, with tumor growth inhibition (TGI) values of 20.8% and 74.1% at dosages of 10 and 30 mg/kg, respectively.
Displayed antitumor effects in A549-xenograft mice, with a TGI value of 51.1% at 30 mg/kg.
Was well tolerated in all of the tested groups, with no mortality or significant loss of body weight.
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Animal Model:Sprague-Dawley (SD) rats (180-220 g)[1]
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Dosage:5 mg/kg for i.v.; 25 mg/kg for p.o. (Pharmacokinetic Analysis)
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Administration:A single intravenous injection and oral administration
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Result:I.v.: T1/2=19.97 h; Cmax=934.38 μg/L; AUC0-∞=8165.8 µg/L•h.
P.o.: T1/2=22.2 h; Cmax=899.5 μg/L; BA=78%.
Chemical Information
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CAS No. 1257628-64-0
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Molecular Weight 532.56
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Formula C29H27F3N6O
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SMILES
O=C(NC1=CC=C(CN2CCN(C)CC2)C(C(F)(F)F)=C1)C3=CC=C(C)C(C#CC4=CN5C(N=C4)=CC=N5)=C3
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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.
Protocols
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
Purity & Documentation
References
[1]. Zhang Z, et al. GZD856, a novel potent PDGFRα/β inhibitor, suppresses the growth and migration of lung cancer cells in vitro and in vivo. Cancer Lett. 2016 May 28;375(1):172-178. [Content Brief]
[2]. Lu X, et al. Synthesis and identification of GZD856 as an orally bioavailable Bcr-AblT315I inhibitor overcoming acquired imatinib resistance. J Enzyme Inhib Med Chem. 2017 Dec;32(1):331-336. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GZD856 Related Classifications
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