JNK-IN-8  1410880-22-6

JNK-IN-8
分子式：C29H29N7O2    分子量：507.59
 
產(chǎn)品描述
JNK-IN-8是*個(gè)，不可逆JNK抑制劑，作用于JNK1, JNK2和 JNK4，IC50分別為 4.7 nM, 18.7 nM 和 1 nM,比作用于MNK2, Fms選擇性高10倍以上，對(duì)c-Kit, Met, PDGFRβ沒(méi)有抑制作用。
靶點(diǎn)
 JNK3  JNK1  JNK2 Kit (V559D,T670I)  Kit (V559D)   
IC50
 1 nM  4.7 nM  18.7 nM  56 nM  92 nM  
體外研究
 JNK-IN-8 inhibits c-Jun phosphorylation in HeLa and A375 cells with EC50 of 486 nM and 338 nM, respectively. JNK-IN-8 shows a dramatic improvement in selectivity and eliminated binding to IRAK1, PIK3C3, PIP4K2C, and PIP5K3. JNK-IN-8 requires Cys116 for JNK2 inhibition. JNK-IN-8 (10 mM) suppresses the IL-1β-stimulated phosphorylation of c-Jun in IL-1R cells, an established substrate of the JNKs. JNK-IN-8 covalently attaches to the JNK isoforms caused a small retardation in the electrophoretic mobility of the JNK isoforms. JNK-IN-8 is discovered to inhibit JNK kinase by broad-based kinase selectivity profiling of a library of acrylamide kinase inhibitors based on the structure of imatinib using the KinomeScan approach. JNK-IN-8 possesses distinct regiochemistry of the 1,4-dianiline and 1,3-aminobenzoic acid substructures relative to imatinib and uses an N,N-dimethyl butenoic acetamide warhead to covalently target Cys154. JNK-IN-8 adopts an L-shaped type I binding conformation to access Cys 154 located toward the lip of the ATP-binding site. 
體內(nèi)研究
 
溶解性
可溶于DMSO
穩(wěn)定性
2年 -20°C粉狀，6月-80°C溶于DMSO