2. JAK/STAT Signaling Protein Tyrosine Kinase/RTK MAPK/ERK Pathway Stem Cell/Wnt PI3K/Akt/mTOR
  3. EGFR p38 MAPK ERK Akt
  4. AZ14289671

AZ14289671 是一种口服有效的、能穿透血脑屏障的酪氨酸激酶 (tyrosine kinase) 抑制剂 (TKI)，专门靶向 EGFR 外显子 20 插入突变 (EGFRExon20Ins) 的非小细胞肺癌 (NSCLC)，同时在很大程度上“豁免”野生型 EGFR，以降低皮疹、腹泻等脱靶毒性。AZ14289671 可抑制下游 MAPK/ERK/AKT 通路，抑制肿瘤细胞增殖、存活和迁移。AZ14289671 可用于研究 NSCLC。

MCE 的所有产品仅用作科学研究或药证申报，我们不为任何个人用途提供产品和服务

AZ14289671

AZ14289671 Chemical Structure

CAS No. : 3101563-22-5

1.  客户无需承担相应的运输费用。

2.  同一机构（单位）同一产品试用装仅限申领一次，同一机构（单位）一年内

     可免费申领三个不同产品的试用装。

3.  试用装只面向终端客户。

规格 是否有货
50 mg   询价  
100 mg   询价  
250 mg   询价  

* Please select Quantity before adding items.

Customer Review

AZ14289671 相关抗体

Top Publications Citing Use of Products

查看 EGFR 亚型特异性产品:

查看所有亚型
EGFR/ErbB1/HER1 ErbB2/HER2 ErbB3/HER3 ErbB4/HER4

查看 p38 MAPK 亚型特异性产品:

查看所有亚型
p38 MAPK Akt1 p38α p38β MAPK13 p38δ p38γ

查看 ERK 亚型特异性产品:

查看所有亚型
ERK ERK1 ERK2 ERK5 ERK8

查看 Akt 亚型特异性产品:

查看所有亚型
Akt Akt1 Akt2 Akt3

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

AZ14289671 is an orally active, blood-brain barrier-penetrant tyrosine kinase (tyrosine kinase) inhibitor (TKI) that specifically targets non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations (EGFRExon20Ins), while largely sparing wild-type EGFR to reduce off-target toxicities such as rash and diarrhea. AZ14289671 inhibits the downstream MAPK/ERK/AKT pathway, suppressing tumor cell proliferation, survival and migration. AZ14289671 can be used for NSCLC research[1].

IC50 & Target[1]

EGFR exon 20 insertion

 

体外研究
(In Vitro)

AZ14289671 (1 μM) 表现出高度的激酶组选择性，仅有一小部分非 EGFR 家族激酶的抑制率超过 50%[1]。
AZ14289671 (2 h) 可强效抑制 EGFRExon20Ins 细胞系中的 EGFR 磷酸化 (平均 IC50 = 17-41 nM)，且在 EGFRWT 细胞系中的活性显著降低 (平均 IC50 = 480-832 nM)，表现出较高的突变体选择性[1]。
AZ14289671 (2 h) 可强效抑制 LXF2478ASV EGFRExon20Ins 细胞中的 ERK 磷酸化，平均 IC50 为 32 nM[1]。
AZ14289671 (10-1000 nmol/L; 2 h, 6 h) 可在处理 2 h 和 6 h 后强效抑制 LXF2478ASV EGFRExon20Ins 细胞中的 MAPK 通路信号传导 (包括 ERK、AKT 和 S6 的磷酸化)[1]。
AZ14289671 (30-1000 nM; 6 h) 可呈剂量依赖性抑制 LXF2478ASV EGFR 外显子 20 插入突变细胞中 MAPK 通路的基因表达[1]。
AZ14289671 (2 h) 可强效抑制 EGFRExon20Ins/T790M、EGFRL858R、EGFRL858R/T790M 和 EGFREx19del 细胞系中的 EGFR 磷酸化 (平均 IC50 = 7-45 nM)，并分别以 75 nM 和 125 nM 的平均 IC50 值抑制 BT-474HER2WT 和 H2170HER2YVMA 细胞中的 HER2 磷酸化[1]。
AZ14289671 (1 μM; 2 h) 具有较低的外排转运体底物倾向，在 MDCKII-MDR1-BCRP 细胞中的外排率为 1.5，在 MDCKI-MDR1 细胞中的外排率为 4.7[1]。

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

AZ14289671 相关抗体:

Western Blot Analysis[1]

Cell Line: LXF2478ASV EGFRExon20Ins cell line
Concentration: 10, 30, 100, 300 and 1000 nM
Incubation Time: 2 h; 6 h
Result: Inhibited downstream EGFR signaling pathways after both 2 and 6 h of treatment, with the most robust inhibition observed for ERK phosphorylation.
Showed evident inhibition of AKT and S6 phosphorylation in a dose-dependent manner.

Real Time qPCR[1]

Cell Line: LXF2478ASV EGFRExon20Ins cell line
Concentration: 30, 100, 300 and 1000 nM
Incubation Time: 6 h
Result: Caused significant, dose-dependent inhibition of MAPK pathway gene expression at 30 nM and above.
Observed significant downregulation for CCND1, DUSP6, EPHA2, EPHA4, ETV5, and SPRY4, correlating with immunoblotting data showing reduced MAPK signaling.
体内研究
(In Vivo)

AZ14289671 (6.25-50 mg/kg；口服；每日 2 次；连续 14 天) 可在 LXF2478ASV 异种移植小鼠模型中诱导剂量依赖性的肿瘤生长抑制[1]。
AZ14289671 (6.25-50 mg/kg；口服；每日 2 次；连续 14 天) 在 H2073WT 异种移植小鼠模型中表现出显著更低的肿瘤生长抑制活性 (最高 TGI 为 62%) 和 EGFR 磷酸化抑制作用[1]。
AZ14289671 (50 mg/kg；口服；每日 2 次；连续 16 天) 可在 A431WT 异种移植小鼠模型中诱导 86% 的 TGI[1]。
AZ14289671 (6.25-50 mg/kg；口服；每日 2 次；持续 28 天) 可在 LU3075DNP 异种移植小鼠模型中诱导剂量依赖性肿瘤生长抑制[1]。
AZ14289671 (25-50 mg/kg；口服；每日 2 次；持续 28 天) 可在 LU0387NPH 异种移植小鼠模型中诱导剂量依赖性肿瘤生长抑制[1]。
AZ14289671 (2 μmol/kg/h；静脉注射；持续输注；4 小时) 可穿过健康大鼠的血脑屏障，其 Kpuu 为 0.17[1]。

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

Animal Model: Hsd:Athymic Nude-Foxn1nu (female; subcutaneous xenograft of LXF2478ASV patient-derived EGFR exon 20 insertion mutant cells)[1]
Dosage: 6.25 mg/kg (twice daily dosing); 12.5 mg/kg (twice daily dosing; single dose); 25 mg/kg (twice daily dosing; single dose); 50 mg/kg (twice daily dosing; single dose)
Administration: p.o.; twice daily; 14 days; p.o.; single dose
Result: Achieved 71% TGI at 6.25 mg/kg, 81% TGI at 12.5 mg/kg, 112% TGI at 25 mg/kg, and 121% TGI after 14 days of twice daily dosing.
Significantly reduced EGFR phosphorylation at 1 and 6 hours post single dose across all dose levels, with >90% reduction observed at 6 hours post 50 mg/kg single dose.
Showed recovery of EGFR phosphorylation at 16 and 24 hours post single dose.
Maintained free plasma concentrations exceeding the IC90 for approximately 6 hours post single dose.
Animal Model: C.B-17/lcrHanHsd-Prkdcscid (female; subcutaneous xenograft of H2073WT EGFR wild-type cells)[1]
Dosage: 6.25 mg/kg (twice daily dosing); 12.5 mg/kg (twice daily dosing; single dose); 25 mg/kg (twice daily dosing; single dose); 50 mg/kg (twice daily dosing; single dose)
Administration: p.o.; twice daily; 14 days; p.o.; single dose
Result: Achieved 47% TGI at 6.25 mg/kg, 53% TGI at 12.5 mg/kg, 55% TGI at 25 mg/kg, and 62% TGI after 14 days of twice daily dosing.
Induced markedly lower EGFR phosphorylation inhibition than in mutant models, with 50 mg/kg inducing ~50% inhibition at 6 hours post single dose.
Failed to reach free plasma concentrations exceeding the IC50 at any dose level post single dose.
Animal Model: C.B-17/lcrHanHsd-Prkdcscid (female; subcutaneous xenograft of A431WT EGFR wild-type cells)[1]
Dosage: 50 mg/kg
Administration: p.o.; twice daily; 16 days
Result: Achieved 86% TGI after 16 days of twice daily dosing.
Was well tolerated with body weight loss < 15%.
Animal Model: BALB/cNj-Foxn1nu/Gpt (female; subcutaneous xenograft of LU3075DNP patient-derived EGFR D770_N771InsPG exon 20 insertion mutant cells)[1]
Dosage: 6.25 mg/kg (twice daily dosing); 12.5 mg/kg (twice daily dosing; single dose); 25 mg/kg (twice daily dosing; single dose); 50 mg/kg (twice daily dosing; single dose)
Administration: p.o.; twice daily; 28 days; p.o.; single dose
Result: Achieved 27% TGI at 6.25 mg/kg, 81% TGI at 12.5 mg/kg, 159% TGI at 25 mg/kg, and 169% TGI after 28 days of twice daily dosing.
Significantly inhibited EGFR phosphorylation at all dose levels post single dose, with > 75% inhibition observed at 1 and 6 hours post 25 mg/kg and 50 mg/kg single doses.
Animal Model: BALB/cNj-Foxn1nu/Gpt (female; subcutaneous xenograft of LU0387NPH patient-derived EGFR N771_H773InsH exon 20 insertion mutant cells)[1]
Dosage: 25 mg/kg; 50 mg/kg
Administration: p.o.; twice daily; 28 days
Result: Achieved 45% TGI at 25 mg/kg and 133% TGI at 50 mg/kg after 28 days of twice daily dosing.
分子量

499.30

Formula

C23H14Cl2F2N6O
CAS 号
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.
纯度 & 产品资料
参考文献

AZ14289671 相关分类

  • 摩尔计算器

  • 稀释计算器

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

质量   浓度   体积   分子量 *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

浓度 (start) × 体积 (start) = 浓度 (final) × 体积 (final)
× = ×
C1   V1   C2   V2
Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

AZ142896713101563-22-5AZ 14289671AZ-14289671EGFRp38 MAPKERKAktEpidermal growth factor receptorErbB-1HER1Extracellular signal regulated kinasesPKBProtein kinase BEGFR L858RHER2 Exon20 insertion (YVMA)non-small cell lung cancerHER2 wild-typeBLKJAK3EGFR Exon20 insertion mutantsEGFR L858R/T790MBMXEGFR Ex19delInhibitorinhibitorinhibit

您最近查看的产品:

Your information is safe with us. * Required Fields.

   产品名称：

  

* 需求量：

* 客户姓名：

 

* Email：

* 电话：

 

* 公司或机构名称：

   留言给我们：

Bulk Inquiry

Inquiry Information

产品名称：
AZ14289671
目录号：
HY-183682
需求量：

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

   产品名称：

  

* Lot #：

* 客户姓名：

 

* Email：

   电话：

 

* 部门：

* 公司或机构名称：

 

   留言给我们：

Request for HNMR Report

We have received your request and will respond to you as soon as possible.

嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z