Crenolanib (CP-868596)670220-88-9

Crenolanib (CP-868596)
分子式：C26H29N5O2分子量：443.54
 
產品描述
Crenolanib (CP-868596)是有效的，選擇性PDGFRα/β抑制劑，Kd為2.1 nM/3.2 nM, 也有效抑制FLT3, 對D842V突變型而不是V561D突變型敏感, 作用于PDGFR比作用于c-Kit, VEGFR-2, TIE-2, FGFR-2, EGFR, erbB2, 和Src選擇性高100倍以上。
靶點
PDGFRα
PDGFRα (D842V)
PDGFRα (purified)
PDGFRβ (purified)
   
IC50
11nM
10 nM
0.9 nM
1.8 nM
   
體外研究
Crenolanib 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 is 135-fold more otent than imatinib against D842V in the isogenic model system, with an IC50 of approximay 10 nM. Crenolanib 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 also inhibits the proliferation of EOL-1 cells with IC50 = 0.2 pM. Crenolanib inhibits the activation of V561D or D842V-mutant kinases expressed in BaF3 cells with IC50 with 85 nM or 272 nM, respectively. Crenolanib 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.Crenolanib is an orally bioavailable, highly potent and selective PDGFR TKI. Crenolanib is a benzimidazole compound that has IC50s of 0.9 nM and 1.8 nM for PDGFRA and PDGFRB, respectively.
體內研究
 
溶解性
DMSO 89 mg/mL，水 <1 mg/mL，乙醇 7 mg/mL
穩定性
2年 -20°C粉狀，6月-80°C溶于DMSO