| In Vitro: |
JNK-IN-8 inhibits phosphorylation of c-Jun, a direct substrate of JNK kinase. JNK-IN-8 inhibits c-Jun phosphorylation in HeLa and A375 cells with EC50 of 486 nM and 338 nM, respectively. JNK-IN-8 also exhibits exceptional selectivity based upon KinomeScan and enzymatic profiling. Cumulatively these combined profiling technologies demonstrate that both JNK-IN-8 and JNK-IN-12 are remarkably selective covalent JNK inhibitors and are appropriate for interrogating JNK-dependent biological phenomena[1]. JNK-IN-8, a selective pan-JNK inhibitor, is discovered to inhibit JNK kinase by broad-base kinase selectivity profiling of a library of acrylamide kinase inhibitors based on the structure of imatinib using the KinomeSca approach. JNK-IN-8 possess distinct regio-chemistry of the 1,4-dianiline and 1,3-aminobenzoic acid substructures relative to imatinib and uses an N,N-dimethyl butenoic actemide warhead to covalently target Cys154. JNK-IN-8 adopts an L-shaped type I binding conformation to access Cys 154 located towards the lip of the ATP-binding site[2]. |
