Karatas Lab
C. Eugene Bennett
Department of Chemistry
Development of Small Molecule Inhibitors of the β-Catenin/BCL9 Protein-Protein Interaction
β-catenin-BCL9 interaction is an important new target in cancer therapy. We aim to develop high affinity (Kd < 100 nM) small molecule inhibitors of the β-catenin-BCL9 interaction using a fragment-based method. Fragment-based screening is often used in drug discovery where low molecular weight (< 300 Da) fragments are screened for protein binding. The fragment hits are then optimized to small molecule inhibitors via stepwise growing or linking the fragments together.
Development of Peptidomimetic Inhibitors of Hox/Pbx Interaction
HoxA9 is a transcription factor highly deregulated in cancer. Pbx is a HoxA9 cofactor and important for HoxA9 function. Inhibitors to compete for HoxA9 binding to Pbx1/3 can block HoxA9 function.
Starting from a HoxA9 peptide, we aim to develop peptidomimetic inhibitors of the HoxA9-Pbx1/3 interaction.
Development of Novel Small-Molecule Calcium Sensitizers for Cardiac Troponin C
The cardiac muscle contraction depends on calcium ion, and is regulated by cardiac troponin. Distruption of cardiac contractility induces hearth failure where the heart is unable to pump enough blood to provide the body with its metabolic demand. Our goal is to strengthen the cardiac tissue via sensitizing it to calcium. Currently we are developing drug-like small molecules that would bind to a hydrophobic patch in cardiac troponin C and increase calcium sensitivity. This could be a new approach to treat heart failure.