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Crenolanib (CP-868596)

现货
Catalog No.
A8307
PDGFR-β有效的选择性抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,300.00
Ship with 10-15 days
5mg
¥ 1,100.00
现货
25mg
¥ 3,300.00
Ship with 10-15 days

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Background

Crenolanib (CP-868596) is a potent, specific, and orally available inhibitor of PDGFRα, PDGFRβ and FLT3 with inhibitor-binding constant (Kd) of 3.2, 2.1, and 0.74 nM, respectively [1].

It has been shown that crenolanib is more potent than quizartinib and sorafenib at blocking FLT3 autophosphorylation and causing cytotoxicity [2]. Crenolanib is confirmed to be100-fold more potent than imatinib at suppressing D842V mutation. In addition, it has been reported that crenolanib inhibits PDGFRα D842V mutation rather than V561D mutation, with IC50 value of 10 nM [1]. In EOL-1 cells, crenolanib also inhibits the FIP1L1-PDGFRA fusion kinase activity (IC50=1 nM) and cell proliferation (IC50= 0.2 pM)[1].

References:
[1] Heinrich MC1, Griffith D, McKinley A, Patterson J, Presnell A, Ramachandran A, Debiec-Rychter M.

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] Galanis A1, Ma H, Rajkhowa T, Ramachandran A, Small D, Cortes J, Levis M. Crenolanib is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants. Blood. 2014 Jan 2;123(1):94-100.

文献引用

1. Ivey MJ, Kuwabara JT, et al. "Platelet-derived growth factor receptor-α is essential for cardiac fibroblast survival." Am J Physiol Heart Circ Physiol. 2019 Aug 1;317(2):H330-H344. PMID:31125253
2. Tang L, Dai F, et al. "RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton." Pharmacol Res. 2018 May 20;133:201-212. PMID:29791873

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt443.54
Cas No.670220-88-9
FormulaC26H29N5O2
SynonymsCP-868596;CP 868596;CP868596
Solubility≥22.2mg/mL in DMSO, ≥2.5 mg/mL in EtOH with ultrasonic, <2.5 mg/mL in H2O
Chemical Name1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine
SDFDownload SDF
Canonical SMILESCC1(COC1)COC2=CC3=C(C=C2)N(C=N3)C4=NC5=C(C=CC=C5N6CCC(CC6)N)C=C4
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1,2]:

细胞系

EOL-1细胞系,BaF3细胞,H1703非小细胞肺癌细胞系

溶解方法

该化合物在DMSO中的溶解度大于22.2mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

50 nM, 48 h

应用

在表达组成型激活的FIP1L1-PDGFRα融合激酶的来自慢性嗜酸粒细胞白血病患者的EOL-1细胞系中,Crenolanib抑制融合癌基因的激酶活性,IC50为21 nM。Crenolanib抑制EOL-1细胞的增殖,IC50为0.2 pM。在表达V561D或D842V-突变型激酶的BaF3细胞中,Crenolanib抑制激酶活化,其IC50分别为85 nM或272 nM。在H1703非小细胞肺癌细胞系中,Crenolanib抑制PDGFRα活化,,IC50为26 nM 。H1703细胞中PDGFRα与含有PDGFRα基因座的4q12区域相比,活性增加24倍。在A549 NSCLC细胞中,Crenolanib(50 nM)降低细胞活力,诱导细胞凋亡,并抑制细胞迁移。

动物实验 [2]:

动物模型

A549细胞异种移植小鼠模型

给药剂量

10 mg/kg和20 mg/kg,2周

应用

Crenolanib(10 mg/kg及20 mg/kg)抑制非小细胞肺癌肿瘤生长并诱导肿瘤细胞凋亡,受体小鼠中crenolanib具有良好的耐受。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Heinrich M C, Griffith D, McKinley A, et al. Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors[J]. Clinical cancer research, 2012, 18(16): 4375-4384.

[2]. Wang P, Song L, Ge H, et al. Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo[J]. OncoTargets and therapy, 2014, 7: 1761.

生物活性

描述 Crenolanib(CP-868596)是PDGFRα/β的一个有效的、选择性抑制剂,对PDGFRα和PDGFRβ的Kd值分别为2.1 nM和3.2 nM。
靶点 PDGFRα PDGFRβ        
IC50 2.1 nM (Kd) 3.2 nM (Kd)        

质量控制

化学结构

Crenolanib (CP-868596)

相关生物数据

Crenolanib (CP-868596)

相关生物数据

Crenolanib (CP-868596)

相关生物数据

Crenolanib (CP-868596)

相关生物数据

Crenolanib (CP-868596)

相关生物数据

Crenolanib (CP-868596)