Crenolanib (CP-868596)
目录号：S2730 别名： ARO 002
Molecular Weight(MW): 443.54
Crenolanib (CP-868596)是一种有效的，选择性PDGFRα/β抑制剂，在CHO细胞中Kd为2.1 nM/3.2 nM，也能有效抑制FLT3，对D842V突变型敏感对V561D突变型不敏感，作用于PDGFR比作用于c-Kit，VEGFR-2，TIE-2，FGFR-2，EGFR，erbB2，和Src的选择性高100倍以上。
客户使用该产品的7个实验数据：
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Combined treatment with Pim and FLT3 inhibitors abrogates growth of Ba/F3-ITD cells. Ba/F3-ITD cells were cultured at 1 × 105/mL with the Pim kinase inhibitor AZD1208 at 1 μmol/L and/or the FLT3 inhibitors quizartinib at 1 nmol/L, sorafenib at 2.5 nmol/L, crenolanib at 20 nmol/L or gilteritinib at 15 nmol/L, or DMSO control. Cell counts measured at 24, 48, and 72 hours were normalized to 0-hour control. Line graphs represent means ± SEM of triplicate values.
Clin Cancer Res, 2018, 24(1):234-247. Crenolanib (CP-868596) purchased from Selleck.
Clin Cancer Res 2013 19(24), 6935-42. Crenolanib (CP-868596) purchased from Selleck.
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NSG mice were inoculated with 1x106 MOLM-13 cells (ffluc+GFP+662 ) and on day 7 were treated with 5x106 FLT3-CAR T-cells alone (CD4+:CD8+ ratio = 1:1), crenolanib alone (15mg/kg body weight as i.p. injection), or both (combination), or were left untreated. The first dose of crenolanib was given on day 7 and mice received 15 doses (Monday-Friday) for 3 consecutive weeks. (a) Serial bioluminesence (BL) imaging to assess leukemia progression/regression in each treatment group.
Leukemia, 2018, 32(5):1168-1179. Crenolanib (CP-868596) purchased from Selleck.
Western blot analysis using 4G10 and anti-FLT3 antibody after immunoprecipitation with anti-FLT3 antibody and Western blot analysis of phospho-ERK (pERK) and ERK performed on whole cell lysates from HB119 and Molm14 cells. Cells were exposed to 100 nM crenolanib for 60 min.
Proc Natl Acad Sci U S A 2014 111(14), 5319-24. Crenolanib (CP-868596) purchased from Selleck.
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Concurrent treatment with Crenolanib and AG1478 enhances apoptosis as monitored by Caspase-3 and PARP-1 cleavage, either in GBM c-CSC or p-CSC, except for p-CSC3. Instead, Crenolanib alone is less effective in inducing apoptosis either in c-CSC or p-CSC pools. High PDGFR α expression is a distinctive feature of p-CSC pools and its expression is de-repressed following AG1478 treatment clearly evident in case 1 and 2, while its expression is downmodulated following Crenolanib treatment in all cases reported.
Mol Cancer 2014 13(1), 247. Crenolanib (CP-868596) purchased from Selleck.
Western blot analysis of CCSMC phenotype-related proteins, including α-SMA, desmin, vimentin, and collagen-I, after treatment with PDGF-BB at 20 ng/ml, Crenolanib at 100 nM. P <0.05 was considered statistically significant.
PLoS One, 2017, 12(2):e0172191. Crenolanib (CP-868596) purchased from Selleck.
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A549 cells were incubated with crenolanib (500 nM) for 48 hours. The nuclei were stained with Hoechst and analyzed using a fluorescent microscope. The representative images are shown. Red arrows indicate apoptotic cells with condensed or fragmented DNA.
Onco Targets Ther 2014 7, 1761-8. Crenolanib (CP-868596) purchased from Selleck.
产品安全说明书
PDGFR抑制剂选择性比较
生物活性
| 产品描述 | Crenolanib (CP-868596)是一种有效的，选择性PDGFRα/β抑制剂，在CHO细胞中Kd为2.1 nM/3.2 nM，也能有效抑制FLT3，对D842V突变型敏感对V561D突变型不敏感，作用于PDGFR比作用于c-Kit，VEGFR-2，TIE-2，FGFR-2，EGFR，erbB2，和Src的选择性高100倍以上。 | |||||||||||||||||||||||
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| 靶点 |
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| 体外研究 |
Crenolanib显著比imatinib有效，能够抑制对imatinib耐药的PDGFRα激酶(D842I，D842V，D842Y，D1842-843IM，和缺失I843)活性。Crenolanib作用于同基因模型系统中D842V，比imatinib有效135倍，IC50大约为10 nM。Crenolanib抑制EOL-1细胞中融合致癌基因的激酶活性，其衍生自慢性噬酸细胞白血病患者，且表达持续活化的FIP1L1- PDGFRα融合激酶，IC50 = 21 nM。Crenolanib也会抑制EOL-1细胞的增殖，IC50 = 0.2 pM。Crenolanib抑制在BaF3细胞中表达的V561D或D842V突变激酶的活化，IC50分别为85 nM或272 nM。Crenolanib抑制H1703非小细胞肺癌细胞系中PDGFRα活化，其能够使包含PDGFRα基因座的4q12区域扩增24倍，IC50为26 nM。[1] Crenolanib是一种口服具有生物活性的，高度有效的，选择性PDGFR TKI。Crenolanib是苯并咪唑化合物，对PDGFRA和PDGFRB的IC50s分别为0.9 nM和1.8 nM。[2] |
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| Cell Data |
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推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)
| 激酶实验： |
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PDGFRα激酶活性的生物化学评估: 中国仓鼠卵巢(CHO)细胞用突变型或野生型PDGFRα瞬时转染，用不同浓度的Crenolanib处理。涉及重组DNA的实验使用2级生物安全条件，根据指南进行。制备来自细胞系的蛋白质裂解物，使用抗PDGFRα抗体进行免疫沉淀反应，然后用于PDGFRα的连续免疫印迹。使用Photoshop软件进行密度测定以量化药物作用，磷酸-PDGFRα的水平标归一化到总蛋白质。密度测定法和增殖实验结果使用Calcusyn 2.1软件分析，以精确测定IC50值。使用Wilcoxon Rank Sum Test比较Crenolanib对给定突变体的IC50值。 |
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| 细胞实验： |
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溶解度 (25°C)
| 体外 | DMSO | 88 mg/mL warmed (198.4 mM) |
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| Ethanol | 7 mg/mL (15.78 mM) | |
| Water | Insoluble | |
| 体内 |
从左到右依次将纯溶剂加入产品，现配现用(数据来自Selleck实验检测而非文献)： 30% PEG400+0.5% Tween80+5% propylene glycol |
30 mg/mL |
* 溶解度检测是由Selleck技术部门检测的，可能会和文献中提供的溶解度有所差异，这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。
化学数据
| 分子量 | 443.54 |
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| 化学式 | C26H29N5O2 |
| CAS号 | 670220-88-9 |
| 稳定性 | powder |
| in solvent | |
| 别名 | ARO 002 |
计算器
摩尔浓度计算器
本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为:
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
*在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。
稀释计算器
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )
在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.
分子量计算器
通过输入化合物的化学式来计算其分子量：
注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2
摩尔浓度计算器
临床试验信息
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
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| NCT01522469 | Completed | Relapsed or Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations | Arog Pharmaceuticals Inc. | July 2012 | Phase 2 |
| NCT01522469 | Completed | Relapsed or Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations | Arog Pharmaceuticals Inc. | July 2012 | Phase 2 |
| NCT01243346 | Completed | D842-related Mutant GIST | Arog Pharmaceuticals Inc. | April 2011 | Phase 2 |
| NCT01229644 | Terminated | Glioma | Arog Pharmaceuticals Inc. | April 2011 | Phase 2 |
| NCT01243346 | Completed | D842-related Mutant GIST | Arog Pharmaceuticals Inc. | April 2011 | Phase 2 |
| NCT01229644 | Terminated | Glioma | Arog Pharmaceuticals Inc. | April 2011 | Phase 2 |
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