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Crenolanib

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Chemical Structure| 670220-88-9 同义名 : CP-868596;CP 868,596;ARO 002
CAS号 : 670220-88-9
货号 : A243601
分子式 : C26H29N5O2
纯度 : 99%+
分子量 : 443.541
MDL号 : MFCD21609260
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(56.36 mM)，配合低频超声，并水浴加热至45℃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：
生物活性
靶点

  • PDGFRβ

    PDGFRβ, Kd:3.2 nM

  • PDGFRα

    PDGFRα, Kd:2.1 nM
描述 The activating mutations of KIT or PDGFRα are important to the pathogenesis of tumors. Crenolanib is a potent class III RTKs inhibitor with Kd values of 3.2nM, 2.1nM and 0.74nM for PDGFRα, PDGFRβ and FLT3 (measured by Kd ELECT screening service), respectively, as well as showed kinase inhibition effect on imatinib-resistant mutation including PDGFRA D842I, D842V, D842Y and DI842-843IM in CHO cells transfected with PDGFRA constructs. Consistent with this, Crenolanib inhibited cell proliferation more potently than imatinib in BaF3 expressed PDGFRA-D842V mutation cells at concentration>50nM[1]. As the potent inhibition by Crenolanib to FLT3, Crenolanib at concentration ranging in 1-50nM dose-dependently inhibited FLT3-ITD AML cell viability and FLT3 signaling, shown as decreased phosphorylation of –FLT3, STAT5, ERK and S6, in MV4-11 and MOLM-13 cells. Administration of Crenolanib at dose of 15mg/kg twice daily (Monday to Friday) for 3 consecutive weeks significantly reduced MOLM-13-RES-luc leukemic infiltration and produce a significant increase in survival in NSG mice engrafted with MOLM-13-RES-luc cells[2].
作用机制 Crenolanib is an selective ATP-competitive inhibitor of class III RTKs, PDGFRα, PDGFRβ and FLT3.[3]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
A549 0-1000 nM Growth Inhibition Assay 24/48/72 h inhibits cell growth dose and time dependently 25328409
A549 500 nM Apoptosis Assay 48 h induces cell apoptosis 25328409
A549 12.5/25/50 nM Function Assay 10 h inhibits cell migration 25328409
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.25mL

0.45mL

0.23mL

11.27mL

2.25mL

1.13mL

22.55mL

4.51mL

2.25mL
参考文献

[1]Heinrich MC, Griffith D, et al. Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res. 2012 Aug 15;18(16):4375-84.

[2]Zimmerman EI, Turner DC, et al. Crenolanib is active against models of drug-resistant FLT3-ITD-positive acute myeloid leukemia. Blood. 2013 Nov 21;122(22):3607-15.