BSJ-04-122

BSJ-04-122 is a potent, selective, covalent dual MKK4/7 inhibitor with IC50 of 4/181 nM, displays excellent kinome selectivity;BSJ-04-122 covalently targets a conserved cysteine (Cys247 for MKK4, and Cys261 for MKK7) located before the DFG motif.SJ-04-122 exhibits potent cellular target engagement and induces robust target-specific downstream effects.In breast cancer cell lines, BSJ-04-122 potently inhibited JNK phosphorylation, BSJ-04-122 significantly decreased levels of T183/Y185 pJNK at 5 uM, resulting in complete inhibition at 10 uM in MDA-MB-231 cells.The combination of the dual MKK4/7 inhibitor BSJ-04-122 with a selective, covalent JNK inhibitor (JNK-IN-8) demonstrated an enhanced antiproliferative activity against triple-negative breast cancer cells.

1. Jie Jiang, et al. Cell Chem Biol. 2020 Dec 17;27(12):1553-1560.e8.