c-Jun N-terminal kinase (JNK) is a protein involved in inflammatory responses throughout the body. Due to its isolation in the heart and brain, and its upregulation in diseases such as Parkinson’s, Alzheimer’s, and stroke, JNK-3 is of particular interest for therapeutic purposes. The goal of the project is to synthesize a novel inhibitor for JNK-3. Structures are chosen through fragment screening approaches. In order to develop small molecules, known reactions are used to synthesize compounds. When a compound has been synthesized, it is sent for biological testing. IC50 results against the protein and the cell are then used to determine activity. When results are returned on basic structures, and if the activity was determined to be high, structure activity relationship (SAR) studies are begun. So far, the library of compounds that have been synthesized have returned with varying activities. Three compounds, in particular, have been promising: 11H-benzo[4,5]imidazo[1,2-a]indol-11-oxime (BIIO), 2-benzothiazolylphenylmethanone oxime (BTAPMO), and 2-(5-trifluoromethyl)-benzothiazolylphenylmethanone oxime (TF-BTAPMO). High activity is determined through in vitro nanomolar IC50 results. Further tests may then be useful in determing how well the compound will function as a medication. As the project continues, the hope is that the most active structure will be discovered.
