GZD856 - CAS:1257628-64-0

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GZD856

目录号 : KM8042 CAS No. : 1257628-64-0

Data Sheet 产品使用指南

GZD856 是一种有效的和具有口服活性的 PDGFRα/β 抑制剂，IC₅₀ 值分别为 68.6 和 136.6 nM。GZD856 也是 Bcr-Abl^T315I 的抑制剂，对天然 Bcr-Abl 和 T315I 突变型的 IC₅₀ 值分别为 19.9 和 15.4 nM。GZD856 具有抗肿瘤活性。

规格	价格	是否有货	数量
5mg		In-stock
10mg		In-stock
25mg		In-stock
50mg		In-stock
100mg		In-stock

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生物活性

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-Abl inhibitor, with IC₅₀s of 19.9 and 15.4 nM for native Bcr-Abl and the T315I mutant. GZD856 formic has antitumor activity.

体外研究

GZD856 (0.0032-10 μM, 72 h) exerts antiproliferative activity against a panel of lung cancer cells.
GZD856 (0.3-3 μM; 24-28 h) induces a dose-dependent G0/G1 phase arrest and apoptosis in H1703 but not A549 cells.
GZD856 (0.1-10 μM; 6 h) dose-dependently inhibits the PDGFRα/β phosphorylation and downstream signaling in H1703 and A549 cells.
GZD856 inhibits the proliferation of K562, K562R (Q252H) and murine Ba/F3 cells ectopically expressing Bcr-Abl and Bcr-Abl, with IC₅₀s of 2.2, 67.0, 0.64 and 10.8 nM, respectively.

Cell Viability Assay

Cell Line:	H1703, A549, Calu-6, 95-D, L-78, HCC827, SPCA-1, H1650, H1299, H522, H332 and H820 NSCLC cells
Concentration:	0.0032-10 μM
Incubation Time:	72 hours
Result:	Inhibited PDGFRα-overexpressing H1703 cells, with an IC₅₀ of 0.25 μM.

Apoptosis Analysis

Cell Line:	H1703 and A549 NSCLC cells
Concentration:	0.3, 1, 3 μM
Incubation Time:	24, 48 hours
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.

Western Blot Analysis

Cell Line:	H1703 and A549 NSCLC cells
Concentration:	0.1-10 μM
Incubation Time:	6 hours
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.

体内研究

GZD856 (10-30 mg/kg, p.o. once daily for 16 d) displays good antitumor activity in both H1703 and A549 lung cancer models and is well tolerated. GZD856 inhibits brain and liver metastasis of lung cancer cells in an A549-Luc orthotopic model.
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-Abl.
GZD856 (5 mg/kg; a single i.v.) exhibits a long half-life (T_1/2=19.97 h), optimal plasma exposure (C_max=934.38 μg/L) and a AUC_0-∞ (8165.8 µg/L•h) in rats.
GZD856 (25 mg/kg; a single p.o.) exhibits a long half-life (T_1/2=22.2 h), optimal plasma exposure (C_max=899.5 μg/L) and a good oral bioavailability (BA=78%) in rats.

Animal Model:	Male CB17-SCID mice implanted with H1703 and A549 cancer cells
Dosage:	10, 30 mg/kg
Administration:	Oral gavage once daily for 16 days
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.

Animal Model:	Sprague-Dawley (SD) rats (180-220 g)
Dosage:	5 mg/kg for i.v.; 25 mg/kg for p.o. (Pharmacokinetic Analysis)
Administration:	A single intravenous injection and oral administration
Result:	I.v.: T_1/2=19.97 h; C_max=934.38 μg/L; AUC_0-∞=8165.8 µg/L•h. P.o.: T_1/2=22.2 h; C_max=899.5 μg/L; BA=78%.

分子式

C₂₉H₂₇F₃N₆O

分子量

532.56

CAS号

1257628-64-0

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.

溶解性数据

In Vitro:

DMSO : 250 mg/mL (469.43 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	1.8777 mL	9.3886 mL	18.7772 mL
5 mM	0.3755 mL	1.8777 mL	3.7554 mL
10 mM	0.1878 mL	0.9389 mL	1.8777 mL

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.08 mg/mL (3.91 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (3.91 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
2.

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.08 mg/mL (3.91 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (3.91 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。