Abstract：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.

张子旸，加州大学伯克利分校，助理教授

北大化院07级本科生，师从杨震、陈家华和唐叶峰教授，于2011年获得学士学位。先后在美国哈佛大学（导师：Andrew Myers）和加州大学旧金山分校（导师：Kevan Shokat）从事博士和博士后研究，其间成果包括新大环内酯抗生素，脑部专一性mTOR抑制剂，专一性的K-Ras突变体抑制剂。2022年夏于加州大学伯克利分校开始独立研究。

UC Berkeley 张子旸实验室致力于基于化学原理的癌症和自免疫疾病领域的新药研发和机理研究。我们结合天然产物化学，有机合成，化学蛋白组学和功能基因组学开发1) 具有化学专一性的新型共价药物和2) 小分子免疫系统控制剂。课题组目前诚聘合成化学或化学生物学训练的博士后1名，开始时间为2022年12月或以后。感兴趣的同学欢迎邮件联系张子旸博士并附CV和2页以内的研究总结。