Special Chemical Biology Seminar
A major challenge in drug design is targeting the disease-driving mechanism without perturbing the normal function of healthy cells. In this talk, I will discuss how to address this challenge by exploiting unique chemical features inexorably linked to the diseased state. I will describe how a highly modular total chemical synthesis of macrolide antibiotics provides a powerful tool for generating variants that overcome antibiotic resistance. I will then focus on cancer cell signaling and new strategies that utilize two therapeutic agents simultaneously to overcome current challenges to oncology drug discovery. I will describe how to target the critical kinase mTOR (mechanistic target of Rapamycin) only in the tissue where cancer is forming and not the rest of the body to enhance therapeutic efficacy and mitigate toxicity in glioblastoma, a lethal form of brain cancer. Lastly, I will report on an approach that leverages the immune system to attack the intracellular "undruggable" oncogene K-Ras (G12C), which can overcome primary drug resistance to current small molecules targeting this oncogene in lung and colon cancer.