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来那替尼 /Neratinib {[allProObj[0].p_purity_real_show]}

货号:A150970 同义名: 来那替尼 (HKI-272) / HKI-272

Neratinib(HKI-272)是一种口服可用的、不可逆的、高度选择性的HER2EGFR抑制剂,对其IC50值分别为59 nM和92 nM。

Neratinib 化学结构 CAS号:698387-09-6
Neratinib 化学结构
CAS号:698387-09-6
Neratinib 3D分子结构
CAS号:698387-09-6
Neratinib 化学结构 CAS号:698387-09-6
Neratinib 3D分子结构 CAS号:698387-09-6
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Neratinib 纯度/质量文件 产品仅供科研

货号:A150970 标准纯度: {[allProObj[0].p_purity_real_show]}
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产品名称 EGFR/ErbB1 ErbB3 ErbB4 HER2/ErbB2 mutant EGFR 其他靶点 纯度
WZ-3146 ++++

EGFR (E746_A750), IC50: 2 nM

EGFR (E746_A750/T790M), IC50: 14 nM

99%+
Daphnetin +

EGFR, IC50: 7.67 μM

PKA,PKC 95%
Lifirafenib ++

EGFR, IC50: 29 nM

+

EGFR(T790M/L858R), IC50: 495 nM

98%
PD168393 ++++

EGFR, IC50: 0.70 nM

99%+
Nazartinib ++

mutant EGFR, Ki: 0.031 μM

++

mutant EGFR, Ki: 0.031 μM

98%
Norcantharidin 98%
CL-387785 ++++

EGFR, IC50: 370 pM

98%
WHI-P154 +++

EGFR, IC50: 4 nM

Src,VEGFR 98%
Tyrphostin A9 +

EGFR, IC50: 460 μM

PDGFR 98%
AG 555 +

EGFR, IC50: 0.7 μM

98%
AG 494 +

EGFR, IC50: 1.2 μM

99%+
AG-556 +

EGFR, IC50: 5 μM

98%
RG13022 +

EGFR, IC50: 4 μM

99%+
Tyrphostin RG 14620 99%+
Vandetanib +

EGFR, IC50: 500 nM

98%
CNX-2006 ++

mutant EGFR, IC50: <20 nM

++

mutant EGFR, IC50: <20 nM

98%
AZD3759 ++++

EGFR (L858R), IC50: 0.2 nM

EGFR (WT), IC50: 0.3 nM

98%
Erlotinib ++++

EGFR, IC50: 2 nM

95%
Saracatinib +++

EGFR (L861Q), IC50: 4 nM

EGFR, IC50: 5 nM

99%+
AG1557 98%
Rociletinib ++

EGFR (wt), Ki: 303.3 nM

EGFR (L858R/T790M), Ki: 21.5 nM

98%
AG490 +

EGFR, IC50: 0.1 μM

98%
Cetuximab ++++

EGFR, Kd: 0.39 nM

98%
Osimertinib ++

WT EGFR, IC50: 12.92 nM

L858R/T790M EGFR, IC50: 11.44 nM

99%
Osimertinib mesylate 98% (Content MsOH 15.2-18.2%)
Chrysophanol mTOR 98%
PD153035 ++++

EGFR, Ki: 5.2 pM

99%+
Olmutinib BTK 99%+
WZ4002 ++++

EGFR (L858R/T790M), IC50: 8 nM

EGFR (L858R), IC50: 2 nM

99%+
Icotinib +++

EGFR, IC50: 5 nM

98+%
Desmethyl Erlotinib HCl ++++

EGFR, IC50: 2 nM

98%
Cyasterone 99%+
PP 3 +

EGFR tyrosine kinase, IC50: 2.7 μM

98%
WZ8040 99%+
(-)-Epigallocatechin Gallate 99%
AG 18 +

EGFR, IC50: 35 μM

99%+
O-Desmethyl gefitinib ++

EGFR, IC50: 36 nM

98%
Falnidamol 99%+
AZ-5104 ++++

EGFR (L858R), IC50: 6 nM

EGFR (L861Q) , IC50: <1 nM

+++

ErbB4, IC50: 7 nM

BRK 99%+
Butein 95%
Genistein 98%
SU5214 +

EGFR, IC50: 36.7 μM

99%+
Naquotinib 99%+
Gefitinib ++

EGFR, IC50: 15.5 nM

+

EGFR (858R/T790M), IC50: 823.3 nM

98%
Theliatinib +++

WT EGFR, IC50: 3 nM

++

EGFR T790M/L858R, IC50: 22 nM

98+%
Lazertinib ++++

WT EGFR, IC50: 76 nM

L858R/T790M EGFR, IC50: 2 nM

++++

Del19/T790M, IC50: 1.7 nM

99%+
Gefitinib-based PROTAC 3 ++

EGFR, DC50: 22.3 nM

99%+
MTX-211 PI3K 98%
(E)-AG 99 99%+
Licochalcone D PARP,Caspase 97%
Zipalertinib +++

EGFR WT, IC50: 8 nM

EGFR (L861Q), IC50: 4.1 nM

+++

HER4, IC50: 4 nM

++++

EGFR L858R, IC50: 2 nM

EGFR(d746-750), IC50: 1.4 nM

97%
JND3229 +++

EGFR WT, IC50: 6.8 nM

++

EGFR L858R/T790M, IC50: 30.5 nM

99%+
Firmonertinib mesylate 99%+
Tyrphostin AG30 99%+
EGFR-IN-12 ++

EGFR, IC50: 21 nM

99%+
Mobocertinib 98%
(Rac)-JBJ-04-125-02 99%
(S)-Sunvozertinib 98%
BLU-945 95%
Poziotinib +++

HER1, IC50: 3.2 nM

++

HER4, IC50: 23.5 nM

+++

HER2, IC50: 5.3 nM

98%
TAK-285 ++

EGFR/HER1, IC50: 23 nM

+

HER4, IC50: 260 nM

++

HER2, IC50: 17 nM

99%+
ARRY-380 analog 98%
Canertinib ++++

EGFR, IC50: 1.5 nM

+++

ErbB2, IC50: 9.0 nM

99%+
Dacomitinib +++

EGFR, IC50: 6.0 nM

+

ErbB4, IC50: 73.7 nM

+

ErbB2, IC50: 45.7 nM

98%
EGFR/ErbB-2/ErbB-4 inhibitor-2 +

ErbB4, IC50: 1.91 μM

+

ErbB2, IC50: 0.08 μM

99%+
(E/Z)-CP-724714 ++

HER2/ErbB2, IC50: 10 nM

98+%
Lapatinib ++

EGFR, IC50: 10.8 nM

+

ErbB4, IC50: 367 nM

+++

ErbB2, IC50: 9.2 nM

98%
AEE788 ++++

EGFR, IC50: 2 nM

+

HER4/ErbB4, IC50: 160 nM

+++

HER2/ErbB2, IC50: 6 nM

c-Fms 98+%
AV-412 free base ++++

EGFR, IC50: 0.75 nM

++

ErbB2, IC50: 19 nM

++++

EGFRL858R/T790M, IC50: 0.51 nM

EGFRT790M, IC50: 0.79 nM

98+%
Neratinib +

EGFR, IC50: 92 nM

+

HER2, IC50: 59 nM

Src 98%
BMS-599626 ++

HER1, IC50: 20 nM

+

HER4, IC50: 190 nM

++

HER2, IC50: 30 nM

99+%
Tucatinib +++

ErbB2, IC50: 8 nM

98%
Allitinib ++++

EGFR, IC50: 0.5 nM

++++

ErbB4, IC50: 0.8 nM

+++

ErbB2, IC50: 3.0 nM

99%
Pelitinib +

EGFR, IC50: 38.5 nM

+

ErbB2, IC50: 1.255 μM

Src,Raf 99%+
Sapitinib +++

EGFR, IC50: 4 nM

+++

ErbB3, IC50: 4 nM

+++

ErbB2, IC50: 3 nM

99%+
CUDC-101 +++

EGFR, IC50: 2.4 nM

++

HER2, IC50: 15.7 nM

HDAC 99%+
Varlitinib +++

ErbB1, IC50: 7 nM

++++

ErbB2, IC50: 2 nM

99%+
Afatinib dimaleate ++++

EGFR (wt), IC50: 0.5 nM

EGFR (L858R/T790M), IC50: 0.4 nM

++

HER2, IC50: 14 nM

98%
Canertinib dihydrochloride +++

EGFR, IC50: 7.4 nM

+++

ErbB2, IC50: 9 nM

98%
Allitinib tosylate ++++

EGFR (T790M/L858R), IC50: 12 nM

EGFR, IC50: 0.5 nM

++++

ErbB4, IC50: 0.8 nM

+++

ErbB2, IC50: 3.0 nM

99%
Tyrphostin AG 528 +

EGFR, IC50: 4.9 μM

+

HER2, IC50: 2.1 μM

98%
Afatinib ++++

EGFR (wt), IC50: 0.5 nM

EGFR (L858R), IC50: 10 nM

++++

ErbB4, IC50: 1 nM

++

HER2, IC50: 14 nM

99%
Pyrotinib dimaleate ++

EGFR, IC50: 0.013 μM

++

HER2, IC50: 0.038 μM

98%
Epertinib HCl ++++

EGFR, IC50: 1.48 nM

+++

HER4, IC50: 2.49 nM

+++

HER2, IC50: 7.15 nM

98%
Tuxobertinib ++++

EGFR, Kd: 0.2 nM

++++

HER2, Kd: 0.76 nM

98%
ALK-IN-1 ++

EGFR(del19), IC50: 36.8 nM

EGFR(C797S/del19), IC50: 138.6 nM

ALK 98+%
Brigatinib +

EGFR(del19), IC50: 39.9 nM

EGFR(C797S/T790M/del19), IC50: 67.2 nM

FLT3,ALK 98%
Avitinib ++++

EGFR L858R/T790M, IC50: 0.18 nM

BTK 99%+
EAI045 97%
Almonertinib 98%
BI-4020 ++++

EGFRdel19 T790M C797S, IC50: 0.2 nM

99%+
EGFR-IN-7 ++++

EGFRL858R/T790M, IC50: 0.19 nM

EGFRd746-750/T790M/C797S, IC50: 0.26 nM

98%
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。
产品名称 HER2 其他靶点 纯度
Poziotinib ++++

HER2, IC50: 5.3 nM

98%
Tyrphostin AG 879 +

HER2-Neu, IC50: 1.0 μM

95%
TAK-285 +

HER2, IC50: 17 nM

99%+
ARRY-380 analog 98%
Canertinib +++

ErbB2, IC50: 9.0 nM

EGFR 99%+
(E/Z)-CP-724714 ++

HER2/ErbB2, IC50: 10 nM

98+%
Lapatinib +++

ErbB2, IC50: 9.2 nM

EGFR 98%
AEE788 ++++

HER2/ErbB2, IC50: 6 nM

EGFR 98+%
Neratinib +

HER2, IC50: 59 nM

EGFR,Src 98%
BMS-599626 +

HER2, IC50: 30 nM

99+%
Mubritinib ++++

HER2/ErbB2, IC50: 6.0 nM

99%+
Tucatinib +++

ErbB2, IC50: 8 nM

98%
Sapitinib ++++

ErbB2, IC50: 3 nM

EGFR 99%+
CUDC-101 ++

HER2, IC50: 15.7 nM

EGFR,HDAC 99%+
Afatinib dimaleate ++

HER2, IC50: 14 nM

98%
Afatinib ++

HER2, IC50: 14 nM

99%
Pertuzumab 95%
Trastuzumab 98%
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。

Neratinib 生物活性

靶点
  • EGFR/ErbB1

    EGFR, IC50:92 nM

  • HER2/ErbB2

    HER2, IC50:59 nM

  • HER2

    HER2, IC50:59 nM

描述 Deregulated expression of receptors EGFR and HER2, two closely related members of the ErbB family of transmembrane receptor tyrosine kinases, has been implicated in the development and malignancy of numerous types of human cancers, making them become a potential target for therapy. Neratinib is a potent inhibitor of HER2 and EGFR with IC50 values of 59nM and 92nM (measured by an autophosphorylation assay using time-resolved fluorometry), respectively. Neratinib>10nM could inhibit autophosphorylation of HER2 in BT474 cells treated for 3h, and EGF-induced autophosphorylation of EGFR in A431. Cell viability assays showed that Neratinib could inhibit HER-2-overexpressing breast cancer cell lines, SK-Br-3 and BT474, with low IC50 values (2nM), as well as EGFR-overexpressed cell line with IC50 value of 81nM, but exhibited much less activation on EGFR- and HER-2-negative cell lines, MDA-MB-435 and SW620. For activation of HER2 can lead to activation of both MAPK pathway and the Akt signal transduction pathways, a test for Neratinib on this two pathway has been done. Neratinib at concentration>2nM caused decreased level of both p-MAPK and p-AKT in BT474 cells. Treatment with Neratinib at concentration>5nM for 12-16h also led to decrease of cyclin D1 and retinoblastoma (Rb), as well as increased p27 in BT474, suggesting the cell cycle block by Neratinib. Oral administration of Neratinib at dose ranging in 10-80mg/kg exhibited anti-tumor activity against various tumor models, including 3T3/neu cells, BT474, SK-OV-3, A431 and MCF-7 xenografts[1].
作用机制 Neratinib binds irreversibly to the ATP binding pocket of HER member receptor tyrosine kinases.[2]

Neratinib 细胞研究

细胞系 浓度 检测类型 检测时间 活动说明 数据源
3T3 Growth Inhibition Assay IC50=700 ± 78 nM 15173008
3T3/neu Growth Inhibition Assay IC50=3 ± 0.14 nM 15173008
A431 Growth Inhibition Assay IC50=81 ± 9 nM 15173008
A549 Growth Inhibition Assay inhibits cell growth in time and dose dependent manner 16818618

Neratinib 动物研究

Dose Rat[3] (p.o.): 5 mg/kg - 100 mg/kg
Administration p.o.
Pharmacokinetics
Animal Rats[3] Dogs[3]
Dose 10 mg/kg 2 mg/kg (male)
Administration p.o. p.o.
Cmax 1.44 μg/ml 35.1 μg/ml
AUC0→t 15.6 ng·hr/ml 323 ng·hr/ml

Neratinib 临床研究

NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT02396108 Breast Cancer Phase 1 Phase 2 Recruiting March 2019 Singapore ... 展开 >> National University Hospital Recruiting Singapore, Singapore, 119228 Contact: Soo Chin Lee    (65) 6779 5555 收起 <<
NCT03182634 Advanced Breast Cancer Phase 2 Recruiting November 2023 United Kingdom ... 展开 >> Royal Marsden Hosital, Sutton Recruiting Surrey, England, United Kingdom, SM2 5PT Royal Bournemouth Hospital Recruiting Bournemouth, United Kingdom Addenbrooke's Hospital Recruiting Cambridge, United Kingdom Royal Devon and Exeter Hospital Recruiting Exeter, United Kingdom Beatson West of Scotland Cancer Centre Recruiting Glasgow, United Kingdom Royal Marsden Hospital Recruiting London, United Kingdom University College Hospital London Recruiting London, United Kingdom Christie Hospital Recruiting Manchester, United Kingdom 收起 <<
NCT00366600 Healthy Phase 1 Completed - United States, Washington ... 展开 >> Northwest Kinetics Tacoma, Washington, United States, 98418 收起 <<

Neratinib 参考文献

[1]Rabindran SK, Discafani CM, et al. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res. 2004 Jun 1;64(11):3958-65.

[2]Feldinger K, Kong A, et al. Profile of neratinib and its potential in the treatment of breast cancer. Breast Cancer (Dove Med Press). 2015 Jun 9;7:147-62.

[3]208051Orig1s000

Neratinib 实验方案

计算器
存储液制备 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.80mL

0.36mL

0.18mL

8.98mL

1.80mL

0.90mL

17.95mL

3.59mL

1.80mL

Neratinib 技术信息

CAS号698387-09-6
分子式C30H29ClN6O3
分子量 557.043
别名 来那替尼 (HKI-272) ;HKI-272
运输蓝冰
存储条件

液体 -20°C:3-6个月-80°C:12个月

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

溶解度

DMSO: 12 mg/mL(21.54 mM),配合低频超声助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO

动物实验配方

30% PEG400+0.5% Tween80+5% propylene glycol+water 5 mg/mL suspension

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