Neratinib
别名: HKI-272 中文名称：来那替尼
Neratinib是一种高度选择性的HER2和EGFR抑制剂，在无细胞试验中IC50分别为59 nM 和 92 nM；微弱抑制KDR和Src，对Akt，CDK1/2/4，IKK-2，MK-2，PDK1，c-Raf和c-Met没有显著的抑制作用。Phase 3。
Neratinib Chemical Structure
CAS: 698387-09-6
产品质控
批次：
纯度：
99.94%
99.94
Neratinib相关产品
| 相关产品 | CP-724714 Sapitinib (AZD8931) Mubritinib (TAK 165) AC480 (BMS-599626) Tyrphostin AG 879 HER2-Inhibitor-1 TAS0728 | 点击展开 |
|---|---|---|
| 相关化合物库 | 激酶抑制剂库 酪氨酸激酶抑制剂分子库 PI3K/Akt 抑制剂库 细胞周期化合物库 血管生成相关化合物库 | 点击展开 |
相关信号通路图
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| SKBR | Growth Inhibition Assay | 0.01-100 nM | 3-7 d | inhibits cell growth in time and dose dependent manner | 21487605 |
| Sf9 | Function assay | 10 mins | Inhibition of human wild type EGFR expressed in Sf9 cells using [gamma32P]-ATP after 10 mins by scintillation counting, IC50 = 0.0025 μM. | 24900643 | |
| Sf9 | Function assay | 10 mins | Inhibition of human EGFR T790M/L858R mutant expressed in Sf9 cells using [gamma32P]-ATP after 10 mins by scintillation counting, IC50 = 0.066 μM. | 24900643 | |
| BAF3 | Function assay | 72 hrs | Inhibition of Tel-fused IGF1R (unknown origin) expressed in mouse BAF3 cells assessed as growth inhibition after 72 hrs by CellTiter-Glo assay, GI50 = 0.19 μM. | 28282122 | |
| BAF3 | Function assay | 72 hrs | Inhibition of Tel-fused INSR (unknown origin) expressed in mouse BAF3 cells assessed as growth inhibition after 72 hrs by CellTiter-Glo assay, GI50 = 0.29 μM. | 28282122 | |
| BAF3 | Growth inhibition assay | 72 hrs | Growth inhibition of mouse BAF3 cells after 72 hrs by CellTiter-Glo assay, GI50 = 1.9 μM. | 28282122 | |
| SKBR3 | Growth Inhibition Assay | IC50=0.0075 ± 0.005 μM | 23816254 | ||
| BT474 | Growth Inhibition Assay | IC50=0.00323 ± 0.00075 μM | 23816254 | ||
| CAL-51 | Growth Inhibition Assay | IC50=1.89 μM | 24009064 | ||
| KPL-1 | Growth Inhibition Assay | IC50=1.89 μM | 24009064 | ||
| BT-549 | Growth Inhibition Assay | IC50=1.14 μM | 24009064 | ||
| MDA-MB-157 | Growth Inhibition Assay | IC50=1.12 μM | 24009064 | ||
| MDA-MB-231 | Growth Inhibition Assay | IC50=1.00 μM | 24009064 | ||
| UACC-732 | Growth Inhibition Assay | IC50=0.65 μM | 24009064 | ||
| HCC1143 | Growth Inhibition Assay | IC50=0.54 μM | 24009064 | ||
| HCC1937 | Growth Inhibition Assay | IC50=0.50 μM | 24009064 | ||
| HCC1395 | Growth Inhibition Assay | IC50=0.49 μM | 24009064 | ||
| HCC1806 | Growth Inhibition Assay | IC50=0.44 μM | 24009064 | ||
| MDA-MB-415 | Growth Inhibition Assay | IC50=0.42 μM | 24009064 | ||
| MCF-7 | Growth Inhibition Assay | IC50=0.41 μM | 24009064 | ||
| MDA-MB-436 | Growth Inhibition Assay | IC50=0.41 μM | 24009064 | ||
| CAMA-1 | Growth Inhibition Assay | IC50=0.37 μM | 24009064 | ||
| MDA-MB-468 | Growth Inhibition Assay | IC50=0.33 μM | 24009064 | ||
| MDA-MB-435 | Growth Inhibition Assay | IC50=0.33 μM | 24009064 | ||
| HCC38 | Growth Inhibition Assay | IC50=0.25 μM | 24009064 | ||
| MDA-MB-134 | Growth Inhibition Assay | IC50=0.17 μM | 24009064 | ||
| T-47D | Growth Inhibition Assay | IC50=0.16 μM | 24009064 | ||
| EFM-19 | Growth Inhibition Assay | IC50=0.11 μM | 24009064 | ||
| HCC1187 | Growth Inhibition Assay | IC50=0.10 μM | 24009064 | ||
| MDA-MB-453 | Growth Inhibition Assay | IC50=0.09 μM | 24009064 | ||
| BT-20 | Growth Inhibition Assay | IC50=0.07 μM | 24009064 | ||
| HCC70 | Growth Inhibition Assay | IC50=0.03 μM | 24009064 | ||
| ZR-75-1 | Growth Inhibition Assay | IC50=0.03 μM | 24009064 | ||
| SUM-190 | Growth Inhibition Assay | IC50=0.01 μM | 24009064 | ||
| SUM-225 | Growth Inhibition Assay | IC50=0.01 μM | 24009064 | ||
| UACC-893 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| UACC-812 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| SK-BR-3 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| MDA-MB-361 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| MDA-MB-175 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| HCC1954 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| HCC1569 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| EFM-192A | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| BT-474 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| MDAMB453 | Growth Inhibition Assay | IC50=1.59 ± 0.179 μM | 23816254 | ||
| KB | Growth Inhibition Assay | IC50=4.13 ± 0.47 μM | 22491935 | ||
| KBv200 | Growth Inhibition Assay | IC50=6.03 ± 0.64 μM | 22491935 | ||
| MCF-7 | Growth Inhibition Assay | IC50=3.30 ± 0.41 μM | 22491935 | ||
| MCF-7/Adr | Growth Inhibition Assay | IC50= 2.88 ± 0.30 μM | 22491935 | ||
| MCF-7 | Growth Inhibition Assay | IC50=3.02 ± 0.34 μM | 22491935 | ||
| MCF-7/FLV1000 | Growth Inhibition Assay | IC50=7.09 ± 0.71 μM | 22491935 | ||
| HL60 | Growth Inhibition Assay | IC50=2.26 ± 0.23 μM | 22491935 | ||
| HL60/Adr | Growth Inhibition Assay | IC50=1.42 ± 0.15 μM | 22491935 | ||
| HEK293/pcDNA3.1 | Growth Inhibition Assay | IC50=5.29 ± 0.53 μM | 22491935 | ||
| HEK293/ABCB1 | Growth Inhibition Assay | IC50=6.91 ± 0.70 μM | 22491935 | ||
| L858R(EGFR) | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| L858R/T790M(EGFR) | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| G776insV_G/C | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| wild-type | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| A775insYVMA | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| G776insV_G/L | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| P780insGSP | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| NCI-H1781 | Growth Inhibition Assay | inhibits cell growth in time and dose dependent manner | 16818618 | ||
| HCC827 | Growth Inhibition Assay | inhibits cell growth in time and dose dependent manner | 16818618 | ||
| H3255 | Growth Inhibition Assay | inhibits cell growth in time and dose dependent manner | 16818618 | ||
| NCI-H1975 | Growth Inhibition Assay | inhibits cell growth in time and dose dependent manner | 16818618 | ||
| A549 | Growth Inhibition Assay | inhibits cell growth in time and dose dependent manner | 16818618 | ||
| 3T3 | Growth Inhibition Assay | IC50=700 ± 78 nM | 15173008 | ||
| 3T3/neu | Growth Inhibition Assay | IC50=3 ± 0.14 nM | 15173008 | ||
| SK-Br-3 | Growth Inhibition Assay | IC50=2 ± 0.18 nM | 15173008 | ||
| BT 474 | Growth Inhibition Assay | IC50=2 ± 0.06 nM | 15173008 | ||
| A431 | Growth Inhibition Assay | IC50=81 ± 9 nM | 15173008 | ||
| MDA-MB-435 | Growth Inhibition Assay | IC50=960 ± 165 nM | 15173008 | ||
| SW620 | Growth Inhibition Assay | IC50=690 ± 84 nM | 15173008 | ||
| SKBR3 | Function assay | Inhibition of human Her2 in SKBR3 cells, EC50 = 0.002 μM. | 18077425 | ||
| BT474 | Function assay | Inhibition of human Her2 in BT474 cells, EC50 = 0.002 μM. | 18077425 | ||
| A431 | Function assay | Inhibition of human Her2 in A431 cells, EC50 = 0.081 μM. | 18077425 | ||
| SW620 | Function assay | Inhibition of human Her2 in SW620 cells, EC50 = 0.69 μM. | 18077425 | ||
| BA/F3 | Cytotoxicity assay | Cytotoxicity against mouse BA/F3 cells expressing EGFR L858R mutant, IC50 = 0.0035 μM. | 19239229 | ||
| BA/F3 | Cytotoxicity assay | Cytotoxicity against mouse BA/F3 cells expressing EGFR L858R/T790M mutant, IC50 = 0.18 μM. | 19239229 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Neratinib是一种高度选择性的HER2和EGFR抑制剂，在无细胞试验中IC50分别为59 nM 和 92 nM；微弱抑制KDR和Src，对Akt，CDK1/2/4，IKK-2，MK-2，PDK1，c-Raf和c-Met没有显著的抑制作用。Phase 3。 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| 靶点 |
|
| 体外研究(In Vitro) | ||||
| 体外研究活性 | Neratinib微弱抑制酪氨酸激酶KDR 和Src，IC50分别为0.8 μM 和 1.4 μM,与 HER-2相比，活性分别弱14和24倍。Neratinib 作用于其他丝-苏氨酸激酶如Akt, cyclin D1/cdk4, cyclin E/cdk2, cyclin B1/cdk1, IKK-2, MK-2, PDK1, c-Raf, 和Tpl-2，以及酪氨酸激酶c-Met没有活性。Neratinib选择性抑制转染 HER-2 (3T3/neu)的3T3细胞增殖,也抑制两种其他 HER-2-过表达的SK-Br-3和 BT474 cells细胞增殖，IC50为 2-3 nM,与未转染的3T3细胞及 EGFR-和 HER-2阴性的MDA-MB-435 和 SW620细胞相比，效果高230倍以上。Neratinib也抑制EGFR-依赖的A431细胞增殖，IC50为81 nM。Neratinib 作用于BT474 细胞，降低HER-2受体自磷酸化， IC50 为5 nM,作用于A431细胞，降低EGF依赖的 EGFR磷酸化，IC50 为3 nM。Neratinib抑制 HER-2，导致下游MAPK和Akt通路受抑制，IC50为2 nM,比Trastuzumab更有效。Neratinib 作用于BT474细胞，抑制cyclin D1表达和 Rb-敏感性基因产物的磷酸化，IC50为9 nM,导致细胞周期停在G1-S期，最终降低细胞增殖。[1] | |||
|---|---|---|---|---|
| 激酶实验 | 使用时间-分辨荧光分析无细胞自磷酸化 | |||
| Neratinib 在DMSO 中制备成10 mg/mL 储液，然后在25 mM HEPES (pH 7.5; 0.002 ng/mL-20 μg/mL)中稀释。纯化重组的HER-2 COOH末端片段(第676-1255位氨基酸) 或EGFR COOH末端片段(第 645-1186位氨基酸)[在100 mM HEPES (pH 7.5) 和50% 甘油中稀释] 与浓度不断增高的Neratinib 在96-孔ELISA板上室温下温育15分钟，孔中含4 mM HEPES (pH 7.5), 0.4 mM MnCl2, 20 μM 钒酸钠，及 0.2 mM DTT 。加入 40 μM ATP 和20 mM MgCl2开始激酶反应，然后在室温下反应1小时。冲洗实验板, 使用铕标记的抗-磷酸化-酪氨酸抗体 (15 ng/每孔)检测磷酸化。冲洗后，使用Victor2 荧光读数仪 (激发波长为340 nm,发射波长为615 nm)测定信号。通过抑制曲线测定抑50%受体磷酸时的Neratinib 浓度 (IC50) 。 | ||||
| 细胞实验 | 细胞系 | 3T3, 3T3/neu, A431, BT474, SK-Br-3, MDA-MB-435, 和SW480 | ||
| 浓度 | 溶于DMSO, 终浓度为0.5 ng/mL-5 μg/mL | |||
| 孵育时间 | 2, 或6天 | |||
| 方法 | 使用不同浓度Neratinib处理细胞 2, 或6 天。使用sulforhodamine B, 一种蛋白结合染料，测定细胞增殖。细胞与10% 三氯乙酸混合，然后使用水广泛冲洗。使用 0.1% sulforhodamine B对细胞进行染色，使用在5% 乙酸中清洗。蛋白-结合染10 mM Tris中,然后在450 nM处测定吸光度。通过抑制曲线测定抑制50% 细胞增殖时的Neratinib 浓度(IC50)。 | |||
| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | p-ERBB2 / ERBB2 / p-ERBB3 / ERBB3 / p-EGFR / p-90RSK pHER2 / HER2 / pAKT / AKT / pERK / ERK |
|
30118499 | |
| Growth inhibition assay | Cell viability |
|
30118499 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | Neratinib每天按10, 20, 40, 和80 mg/kg剂量口服处理给药3T3/neu 移植瘤，显著抑制生长，分别抑制34%, 53%, 98%, 和 98%。Neratinib每天按40 mg/kg剂量处理，1小时内抑制 84% HER-2磷酸化，相应地，Neratinib 每天按5, 10, 和 40 mg/kg剂量处理BT474 移植瘤，抑制分别为70-82%, 67%, 和 93%。Neratinib也有效作用于SK-OV-3移植瘤，每天按 5 和 60 mg/kg剂量处理，抑制分别为 31% 和85% 。Neratinib作用于EGFR依赖性A431移植瘤比作用于HER-2-依赖性肿瘤效果弱, 每天按5 和 20 mg/kg剂量处理，抑制分别为32%和44%。Neratinib作用于表达低水平HER-2和EGFR的MCF-7和 MX-1移植瘤几乎没有活性, 每天按80 mg/kg剂量处理抑制只为28%，说明Neratinib 选择性作用于表达HER-2或EGFR的细胞。[1] | |
|---|---|---|
| 动物实验 | Animal Models | 皮下移植3T3/neu, BT474, MCF-7, 或 SK-OV-3 细胞的雌性无胸腺裸鼠 |
| Dosages | ~80 mg/kg/day | |
| Administration | 口服饲喂 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT05388149 | Recruiting | Breast Cancer|HER2-positive Breast Cancer |
University Health Network Toronto |
December 6 2022 | Phase 2 |
| NCT05252988 | Recruiting | Early-stage Breast Cancer|HER2 Positive Breast Cancer|Hormone Receptor Positive |
Spanish Breast Cancer Research Group|Puma Biotechnology Inc.|Pierre Fabre Laboratories |
August 31 2022 | Phase 2 |
| NCT04856475 | Withdrawn | Breast Cancer|Brain Metastases |
Jules Bordet Institute |
November 24 2021 | Phase 2 |
| NCT04781374 | Withdrawn | Metastatic Prostate Adenocarcinoma|Castration-resistant Prostate Cancer|Prostate Cancer|Prostate Cancer Metastatic |
Beth Israel Deaconess Medical Center|Puma Biotechnology Inc.|Dana-Farber Cancer Institute |
May 21 2021 | Phase 2 |
化学信息&溶解度
| 分子量 | 557.04 | 分子式 | C30H29ClN6O3 |
| CAS号 | 698387-09-6 | SDF | Download Neratinib SDF |
| Smiles | CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)C=CCN(C)C | ||
| 储存条件(自收到货起) | |||
|
体外溶解度 |
DMSO : 6 mg/mL ( (10.77 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : Insoluble Ethanol : Insoluble |
摩尔浓度计算器 |
|
体内溶解配方 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | |||||
实验计算
动物体内配方计算器（澄清溶液）
第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）
mg/kg
g
μL
只
第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
计算结果：
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
技术支持
在订购、运输、储存和使用我们的产品的任何阶段，您遇到的任何问题，均可以通过拨打我们的热线电话400-668-6834，或者技术支持邮箱tech@selleck.cn，直接联系到我们。我们会在24小时内尽快联系您。
如果有其他问题，请给我们留言。
* 必填项
Tags: buy Neratinib | Neratinib supplier | purchase Neratinib | Neratinib cost | Neratinib manufacturer | order Neratinib | Neratinib distributor
