Crenolanib (CP-868596)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Crenolanib(CP-868596)是PDGFRα、PDGFRβ和FLT3有效的、特定的和普遍适用的抑制剂,对于三者的Kd值分别为3.2 nM、2.1 nM和0.74 nM[1]。
已被证明Crenolanib比Quizartinib和索拉非尼在阻止FLT3自身磷酸化和导致细胞毒性方面更有效[2]。Crenolanib抑制D842V突变能力是伊马替尼的100倍。此外,据报道,Crenolanib可抑制PDGFRαD842V突变(IC50=10 nM)而不能抑制V561D突变[1]。在EOL-1细胞中,Crenolanib还能抑制FIP1L1-PDGFRA融合激酶活性(IC50 = 1 nM)和细胞增殖(IC50 = 0.2 pM)[1]。
参考文献:
[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. Crenolanibis a potent inhibitor of FLT3 with activity against resistance-conferring point mutants. Blood.2014 Jan 2;123(1):94-100.
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
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 443.54 |
Cas No. | 670220-88-9 |
Formula | C26H29N5O2 |
Synonyms | CP-868596;CP 868596;CP868596 |
Solubility | ≥22.2 mg/mL in DMSO; insoluble in H2O; ≥2.5 mg/mL in EtOH with ultrasonic |
Chemical Name | 1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine |
SDF | Download SDF |
Canonical SMILES | CC1(COC1)COC2=CC3=C(C=C2)N(C=N3)C4=NC5=C(C=CC=C5N6CCC(CC6)N)C=C4 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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. |
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) |
质量控制和MSDS
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