Crenolanib (CP-868596)

An inhibitor of PDGFRα/β and FLT3

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5mg

￥1025.00

820.00

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25mg

￥3012.00

2410.00

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货号: ajci14054
CAS: 670220-88-9
别名: [1-[2-[5-(3-甲基氧杂环丁烷-3-基甲氧基)苯并咪唑-1-基]喹啉-8-基]哌啶-4-基]胺,CP-868596;CP 868596;CP868596
分子式: C26H29N5O2
分子量: 443.54
纯度: >98%
溶解度: ≥ 22.2mg/mL in DMSO, ≥ 2.5 mg/mL in EtOH with ultrasonic
储存: Store at -20°C
库存: 现货

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].

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. Crenolanib?is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants. Blood.?2014 Jan 2;123(1):94-100.

Protocol

Cell experiment [1,2]:
Cell lines	EOL-1 cell line, BaF3 cells, H1703 non-small cell lung cancer cell line
Preparation method	The solubility of this compound in DMSO is >22.2mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition	50 nM, 48 h
Applications	In EOL-1 cell line derived from a patient with chronic eosinophilic leukemia and expressed the constitutively activated FIP1L1-PDGFRα fusion kinase, Crenolanib inhibited the kinase activity of the fusion oncogene with IC50 of 21 nM. Crenolanib inhibited the proliferation of EOL-1 cells with IC50 of 0.2 pM. Crenolanib inhibited the activation of V561D or D842V-mutant kinases expressed in BaF3 cells with IC50 of 85 nM or 272 nM, respectively. Crenolanib inhibited PDGFRα activation in H1703 non-small cell lung cancer cell line which has 24-fold amplification of the 4q12 region that contained the PDGFRα locus, with IC50 of 26 nM. Crenolanib (50 nM) decreased A549 NSCLC cell viability, induced apoptosis in A549 NSCLC cells, and inhibited cell migration in A549 NSCLC cells.
Animal experiment [2]:
Animal models	A549 cells xenograft mouse model
Dosage form	10 mg/kg and 20 mg/kg, 2 weeks
Application	Crenolanib (10 mg/kg and 20 mg/kg) suppressed non-small-cell lung cancer tumor growth and induced tumor cell apoptosis, and the dosage of crenolanib applied was well tolerated by recipient mice.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
参考文献: [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.