Neratinib

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Neratinib

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

698387-09-6

包装与价格：

包装	价格(元)
10 mM * 1 mL in DMSO	电议
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议
200mg	电议
500mg	电议
1 g	电议

产品名称

来那替尼
HKI-272

产品介绍

Neratinib (HKI-272) 是一种具有口服活性的、不可逆的、高选择性的HER2和EGFR抑制剂，IC₅₀值分别为 59 nM 和 92 nM。

生物活性

Neratinib (HKI-272) is an orally available, irreversible, highly selectiveHER2andEGFRinhibitor withIC₅₀s of 59 nM and 92 nM, respectively^[1].

IC₅₀& Target^[1]

HER2

59 nM (IC₅₀)

EGFR

92 nM (IC₅₀)

体外研究
(In Vitro)

Neratinib displays no activity against other serine-threonine kinases such as Akt, cyclin D1/cdk4, cyclin E/cdk2, cyclin B1/cdk1, IKK-2, MK-2, PDK1, c-Raf, and Tpl-2, as well as the tyrosine kinase c-Met^[1].
Neratinib (0.5 ng/mL–5 μg/mL, 2 days) inhibits the proliferation of cell lines that show high levels of HER-2 (3T3/neu, SK-Br-3, and BT474) and is much less active in cell lines that express neither HER-2 nor EGFR (3T3, MDA-MB-435, and SW620)^[1].
Neratinib (0-2 nM, 12-16 h) arrests BT474 cell cycle at G1-S phase^[1].
Neratinib results in the inhibition of MAPK and Akt phosphorylation, down-regulation of cyclin D1 levels, and induction of p27^[1].

Cell Proliferation Assay^[1]

Cell Line:	3T3, 3T3/neu, SK-Br-3, BT 474, A431, MDA-MB-435 and SW620
Concentration:	0.5 ng/mL–5 μg/mL
Incubation Time:	2 days (6 days for BT474)
Result:	Inhibited cell proliferation with IC₅₀values of 700 ± 78, 3 ± 0.14, 2 ± 0.18, 2 ± 0.06, 81± 9, 960 ± 165 and 690 ± 84 nM against 3T3, 3T3/neu, SK-Br-3, BT 474, A431, MDA-MB-435 and SW620 cells, respectively.

Western Blot Analysis^[1]

Cell Line:	BT474 or A431 cells
Concentration:	0, 2, 10, 50, 100 and 200 nM
Incubation Time:	3 h
Result:	Decreased ligand-independent receptor phosphorylation by 50% (IC₅₀) at 5 nM in BT474 cells, repressed EGF-dependent phosphorylation of EGFR in A431 cells at a comparable dose (IC₅₀= 3 nM). Effectively repressed phosphorylation of MAPK and Akt in BT474 cells.

Cell Cycle Analysis^[1]

Cell Line:	BT474
Concentration:	0–2 nM
Incubation Time:	12–16 h
Result:	Blocked cell cycle progression, causing a G1-S arrest, a 50% decrease in the number of cells in the S (DNA synthesis) phase of the cell cycle was observed at a concentration of 2 nM.

体内研究
(In Vivo)

Neratinib (HKI-272) (0-80 mg/kg/day; i.g.; 42 days) shows anticancer activities against cancer cells that expresses high levels of HER-2 or EGFR^[1].

Animal Model:	Female athymic (nude) mice, tumor xenograft^[1]
Dosage:	10, 20, 40, 60 or 80 mg/kg/day
Administration:	Gavage, 42 days
Result:	Reduced tumor growth in a dose-dependent manner in 3T3/neu, BT474, SK-OV-3 and A431 xenografts, but was o inactive in xenografts of MX-1 and MCF-7. Inhibited phosphorylation of HER-2 in BT474 xenografts.

Clinical Trial

分子量

557.04

性状

Solid

Formula

C₃₀H₂₉ClN₆O₃

CAS 号

698387-09-6

中文名称

来那替尼

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

溶解性数据

In Vitro:

DMSO : 13.33 mg/mL(23.93 mM;Need ultrasonic)

配制储备液

浓度溶剂体积质量

1 mg

5 mg

10 mg

1 mM	1.7952 mL	8.9760 mL	17.9520 mL
5 mM	0.3590 mL	1.7952 mL	3.5904 mL
10 mM	0.1795 mL	0.8976 mL	1.7952 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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

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： 0.5% MC 0.5%Tween-80
Solubility: 3.33 mg/mL (5.98 mM); Suspended solution; Need ultrasonic
2.
请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline)
Solubility: 2 mg/mL (3.59 mM); Suspended solution; Need ultrasonic
此方案可获得 2 mg/mL (3.59 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。
以 1 mL 工作液为例，取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
3.
请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline
Solubility: ≥ 0.83 mg/mL (1.49 mM); Clear solution
此方案可获得 ≥ 0.83 mg/mL (1.49 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 8.3 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。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液

*以上所有助溶剂都可在本网站选购。