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.
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- No. CAS: 1257628-64-0
- Fòrmula: C29H27F3N6O
- Peso molecular:532.56
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Actividad biológica
Descripciòn
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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.
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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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No. CAS 1257628-64-0
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Peso molecular 532.56
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Fòrmula 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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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[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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