Summary: Our research focuses on using synthetic organic chemistry to help solve problems associated with the treatment of cancer. For example, one project involves synthesizing small molecule inhibitors (SMIs) of a pro-metastatic inflammatory cytokine. Also, to study their DNA binding and anticancer properties, my research students synthesized—using a 20-step sequence—aziridinomitosenes, compounds related to the mitomycin family of antitumor agents. In vitro experiments with a variety of cancer cell cultures demonstrated that the new aziridinomitosenes form DNA interstrand crosslinks and also crosslink protein to DNA. My students and I also partnered with a small pharmaceutical company to synthesize and study potentially non-cardiotoxic doxorubicin analogs. We prepared and obtained data relevant to one DOX analog that recently completed Phase 2 clinical trials, and another is undergoing pre-clinical experiments.
Minimum Classes: N/A
Projects: Students working in Dr. Warner’s lab will aim to synthesize analogs of lead small molecule inhibitors (SMIs) that have been shown to interrupt signaling of a pro-metastatic cytokine. Students will help assemble and analyze a small library of compounds related to the leads to establish structure-activity relationships and identify optimized next-generation SMIs. The binding mode and affinity of each lead will be determined using nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetery (ITC). Also, the extent of inhibition of OSM signaling in breast cancer cell lines will be characterized, as will the impact of the SMIs on invasive potential. Students will gain significant experience in drug development, especially in the organic chemistry techniques required to prepare new medicines.