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| 活性类型 | 活性值-log(M) | 作用机制 | 期刊 | 参考文献(PubMed IDs) |
|---|
AZD4547, 成纤维细胞生长因子受体 1 抑制剂；成纤维细胞生长因子受体 2 抑制剂；成纤维细胞生长因子受体 3 抑制剂；成纤维细胞生长因子受体 4 抑制剂；胰岛素样生长因子 I 受体抑制剂；激酶插入域受体抑制剂
有货
为什么选择此级别
Moligand™ 级 ，适用于对基线干扰要求严格的色谱和分析工作流程。
储存与运输
-80℃储存。特低温运输 。请查阅批次 COA 获取详细规格。
质量文档
SDS、COA、产品数据表及规格说明书均可下载。可通过批号查询获取批次 COA。
文献证明
在色谱分析、有机合成和交叉偶联反应领域已被 1 篇同行评审文献引用。
概述
AZD4547是一种新型选择性的FGFR抑制剂，靶向作用于FGFR1/2/3，IC50为0.2 nM/2.5 nM/1.8 nM，对FGFR4， VEGFR2(KDR)具有微弱的作用活性，对IGFR， CDK2和p38几乎没有作用活性。Phase 2/3。A novel selective FGFR inhibitor targeting FGFR1, FGFR2, and FGFR3.
Information
AZD4547 (ABSK 091) is a novel selectiveFGFRinhibitor targeting FGFR1/2/3 withIC50of 0.2 nM/2.5 nM/1.8 nM in cell-free assays, weaker activity against FGFR4, VEGFR2(KDR), and little activity observed against IGFR, CDK2, and p38. Phase 2/3.
In vitro
Compared to FGFR1-3, AZD4547 displays weaker activity against FGFR4 with IC50 of 165 nM. AZD4547 only inhibits recombinant VEGFR2 (KDR) kinase activity with IC50 of 24 nM, in the in vitro selectivity test against a diverse panel of representative human kinases. AZD4547 at 0.1 μM exhibits no activity against a range of recombinant kinases including ALK, CHK1, EGFR, MAPK1, MEK1, p70S6K, PDGFR, PKB, Src, Tie2, and PI3-kinase. Consistently, the potent selectivity of AZD4547 for FGFR1-3 over FGFR4, IGFR, and KDR is also observed in cellular phosphorylation assays. AZD4547 has potent in vitro antiproliferative activity only against tumor cell lines expressing deregulated FGFRs such as KG1a, Sum52-PE, and KMS11 with IC50 of 18-281 nM, and is inactive against MCF7 as well as more than 100 additional tumor cell lines. AZD4547 treatment potently inhibits FGFR and MAPK phosphorylation in human tumor cell lines in a dose-dependent manner. AZD4547 also potently inhibits the phosphorylation of FRS2 and PLCγ, downstream markers of FGFR signaling. Notably, AZD4547 affects the AKT phosphorylation in the breast cell lines, MCF7 and Sum52-PE but not in KG1a and KMS11 lines. AZD4547 treatment significantly induces apoptosis in Sum52-PE and KMS11 cells, dramatically increases G1 arrest but not apoptosis in KG1a cells, and has no effect on cell cycle distribution or apoptosis in MCF7 cells.
In vivo
Oral administration of AZD4547 at 3 mg/kg twice daily in mice bearing KMS11 tumors results in significant tumor growth inhibition of 53% when compared with vehicle-treated controls, and AZD4547 at 12.5 mg/kg once daily or 6.25 mg/kg twice daily leads to complete tumor stasis, which is associated with dose proportional pharmacodynamic modulation of phospho-FGFR3 and reduced KMS11 tumor cell proliferation. Moreover, oral administration of AZD4547 at 12.5 mg/kg once daily results in 65% tumor growth inhibition in the FGFR1-fusion KG1a xenograft model. At efficacious dose levels, AZD4547 does not exhibit antiangiogenic effects. AZD4547 has no significant effect on blood pressure and therefore lacks in vivo anti-KDR activity. Consistently, dosing of 6.25 mg/kg orally twice daily AZD4547 is inactive in the cediranib-sensitive xenograft models including Calu-6, HCT-15 and LoVo.
Cell Data
cell lines：HCC1806 cells
Concentrations：Dissolved in DMSO, final concentrations ~1 μM
Incubation Time：72 hours
Powder Purity:≥99%
规格
英文别名
ABSK 091 | N-(5-(3,5-dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3S,5R)-3,5-dimethylpiperazin-1-yl)benzamide
规格或纯度
Moligand™, 10mM in DMSO
英文名称
AZD4547
生化机理
AZD4547 (ABSK 091) 是一种新型选择性表皮生长因子受体抑制剂，靶向表皮生长因子受体 1/2/3，在无细胞实验中的 IC50 为 0.2 nM/2.5 nM/1.8 nM，对表皮生长因子受体 4、血管内皮生长因子受体 2(KDR) 的活性较弱，对表皮生长因子受体、CDK2 和 p38 的活性很小。2/3 期。
储存条件
-80℃储存
运输条件
特低温运输
作用类型
抑制剂
作用机制
成纤维细胞生长因子受体 1 抑制剂；成纤维细胞生长因子受体 2 抑制剂；成纤维细胞生长因子受体 3 抑制剂；成纤维细胞生长因子受体 4 抑制剂；胰岛素样生长因子 I 受体抑制剂；激酶插入域受体抑制剂
名称和识别符
EC号
681-057-4
分子类型
小分子
Isomeric SMILES
C[C@@H]1CN(C[C@@H](N1)C)C2=CC=C(C=C2)C(=O)NC3=NNC(=C3)CCC4=CC(=CC(=C4)OC)OC
分子量
463.57
Reaxy-Rn
28755157
Reaxys-RN link address
https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=28755157&ln=
技术文档
高级数据
关联靶点（人）
FGFR1
Tclin
成纤维细胞生长因子受体 1(Fibroblast growth factor receptor 1)
(16 活性数据)
FGFR2
Tclin
成纤维细胞生长因子受体 2(Fibroblast growth factor receptor 2)
(15 活性数据)
FGFR4
Tclin
成纤维细胞生长因子受体 4(Fibroblast growth factor receptor 4)
(1 活性数据)
FGFR3
Tclin
成纤维细胞生长因子受体 3(Fibroblast growth factor receptor 3)
(12 活性数据)
IGF1R
Tclin
胰岛素类生长因子 1 受体(Insulin-like growth factor 1 receptor)
(1 活性数据)
KDR
Tclin
血管内皮生长因子受体 2(Vascular endothelial growth factor receptor 2)
(4 活性数据)
化学和物理性质
溶解性
Solubility (25°C) In vitro DMSO: 49 mg/mL (198.13 mM); Ethanol: 49 mg/mL (198.13 mM); Water: Insoluble;
安全和危险性（GHS）
信号词
危险
危险声明
H301: 吞咽会中毒
H372: 通过长时间或反复暴露对器官造成损害
质检证书（CoA,COO,BSE/TSE 和分析图谱)
C of A & Other Certificates(BSE/TSE, COO):
输入批号以搜索分析图谱:
此产品的引用文献
溶液计算器
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