GZD856 formic|cas:2804039-78-7|西域试剂

GZD856 formic,98.06%

产品编号：Bellancom-101489A| CAS NO：2804039-78-7| 分子式：C₃₀H₂₉F₃N₆O₃| 分子量：578.58

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货号	价格	库存与货期
Bellancom-101489A	￥4000.00	杭州北京（现货）
Bellancom-101489A	￥6800.00	杭州北京（现货）
Bellancom-101489A	￥13500.00	杭州北京（现货）
Bellancom-101489A	￥22000.00	杭州北京（现货）
Bellancom-101489A	￥34000.00	杭州北京（现货）

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GZD856 formic

产品介绍

GZD856 formic 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 formic 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 formic 具有抗肿瘤活性。

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^T315I 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^WT and Bcr-Abl^T315I, with IC₅₀s of 2.2, 67.0, 0.64 and 10.8 nM, respectively.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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
(In Vivo)

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^T315I.
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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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%.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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%.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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%.

性状

Solid

溶解性数据

In Vitro:

DMSO : 100 mg/mL (172.84 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	1.7284 mL	8.6418 mL	17.2837 mL
5 mM	0.3457 mL	1.7284 mL	3.4567 mL
10 mM	0.1728 mL	0.8642 mL	1.7284 mL

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

-20°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

参考文献