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Crenolanib

产品号 S2730 公司名称 Selleck Chemicals
CAS号 670220-88-9 公司网站 http://www.selleckchem.com
分子式 C26H29N5O2 电 话 (877) 796-6397
分子量 443.54076 传 真 (832) 582-8590
纯 度 电子邮件 sales@selleckchem.com
保 存 -20°C Chembase数据库ID: 73218

产品价格信息

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产品别名

标题
Crenolanib
IUPAC标准名
1-(2-{5-[(3-methyloxetan-3-yl)methoxy]-1H-1,3-benzodiazol-1-yl}quinolin-8-yl)piperidin-4-amine
IUPAC传统名
crenolanib
别名
CP-868569)

产品登记号

CAS号 670220-88-9

产品性质

作用靶点 VEGFR-PDGFR
成盐信息 Free Base
保存条件 -20°C

产品详细信息

详细说明 (English)
Research Area
Description Glioma, Cancer
Biological Activity
Description Crenolanib (CP-868569) is a potent and selective inihibitor of PDGFRα with IC50 of 10 nM in PDGFRα over-expressed CHO cells.
Targets PDGFRα PDGFRα (D842V) PDGFRα (purified) PDGFRβ (purified)
IC50 11nM 10 nM [1] 0.9 nM 1.8 nM [2]
In Vitro Crenolanib (CP-868569) is significantly more potent than imatinib in inhibiting the kinase activity of imatinib-resistant PDGFRα kinases (D842I, D842V, D842Y, D1842-843IM, and deletion I843). Crenolanib (CP-868569) is 135-fold more otent than imatinib against D842V in the isogenic model system, with an IC50 of approximately 10 nM. Crenolanib (CP-868569) inhibits the kinase activity of the fusion oncogene in EOL-1 cell line, which is derived from a patient with chronic eosinophilic leukemia and expresses the constitutively activated FIP1L1- PDGFRα fusion kinase, with IC50 = 21 nM. Crenolanib (CP-868569) also inhibits the proliferation of EOL-1 cells with IC50 = 0.2 pM. Crenolanib (CP-868569) inhibits the activation of V561D or D842V –mutant kinases expressed in BaF3 cells with IC50 with 85 nM or 272 nM, respectively. Crenolanib (CP-868569) inhibits PDGFRα activation in H1703 non-small cell lung cancer cell line which has 24-fold amplification of the 4q12 region that contains the PDGFRα locus, with IC50 with 26 nM. [1] CP-868,596 is an orally bioavailable, highly potent and selective PDGFR TKI. CP-868,596 is a benzimidazole compound that has IC50s of 0.9 nM and 1.8 nM for PDGFRA and PDGFRB, respectively. [2]
In Vivo
Clinical Trials
Features
Protocol
Kinase Assay [1]
Biochemical Assessment of PDGFRα Kinase Activity Chinese hamster ovary (CHO) cells are transiently transfected with mutated or wild type PDGFRα constructs and treated with various concentrations of Crenolanib (CP-868569). Experiments involving recombinant DNA are performed using biosafety level 2 conditions in accordance with guidelines. Protein lysates from cell lines are prepared and subjected to immunoprecipitation using anti-PDGFRα antibodies followed by sequential immunoblotting for PDGFRα. Densitometry is performed to quantify drug effect using Photoshop software, with the level of phosphor- PDGFRα normalized to total protein. Densitometry and proliferation experimental results are analyzed using Calcusyn 2.1 software to mathematically determine the IC50 values. The Wilcoxon Rank Sum Test is used to compare the IC50 values of Crenolanib (CP-868569) for a given mutation.
Cell Assay [1]
Cell Lines EOL-1 cell line
Concentrations 0 – 20 pM
Incubation Time 72 hours
Methods Cells are added to 96-well plates at densities of 20, 000 cells/well and incubated with Crenolanib (CP-868569) for 72 hours before measuring cellular proliferation using a 2,3-bis[2-methoxyl-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT)-based assay.
References
[1] Heinrich MC, et al, Clin Cancer Res, 2012, Jun 27.
[2] Heinrich M, et al, AACR, 2011, Abstract 3586.