c-Jun N-Terminal Kinases (JNKs), members of the Mitogen-Activated Protein
Kinase (MAPK) signaling pathway, play a key role in the pathogenesis of many diseases
including cancer, inflammation, Parkinson’s disease, Alzheimer’s disease, cardiovascular
disease, obesity, and diabetes. Therefore, JNKs represent new and excellent target by therapeutic
agents. Many JNK inhibitors based on different molecular scaffolds have been
discovered in the past decade. However, only a few of them have advanced to clinical trials.
The major obstacle for the development of JNK inhibitors as therapeutic agents is the JNKisoform
selectivity. In this review, we describe the recent development of JNK inhibitors,
including ATP competitive and ATP non-competitive (allosteric) inhibitors, bidentatebinding
inhibitors and dual inhibitors, the challenges, and the future direction of JNK inhibitors
as potential therapeutic agents.