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University of Wisconsin-Madison

VIRTUAL PharmSci Seminar – Yaoqiu Zhu, PhD

October

22,

2021

Pharmaceutical Sciences Seminar Series

Remdesivir (Veklury), (−)-Pavidolide B to Clopidogrel (Plavix), Translational and Integrative Organic Synthesis for Medicine, Science and Humanity

(Drug DISCOVERY Specific Seminar)

Organic synthesis studies, especially those for the development of essential medicines, constitute the core of chemical science. This seminar will introduce three (3) of such studies developed from our young group at UT-El Paso. The first one is our very recent endeavor on COVID-19 medicine, remdesivir (Veklury). To address its process challenge and global supply shortage, efficient new synthetic routes have been under development. Our flexible new routes can also yield structural analogs for antiviral drug development. The second part will briefly introduce our recently accomplished 4-step total synthesis of (−)-pavidolide B, a complex tetracyclic marine diterpenoid. The new route has also delivered three stereoisomers of the false-bioactive natural product, and they have demonstrated exciting anticancer profiles. This work showcases that facile and flexible total synthesis can be developed to facilitate modern drug discovery. The third story is solving the long-overdue clinical conundrums of the blockbuster antiplatelet prodrug clopidogrel (Plavix). Our systematic studies have not only elucidated the biochemical mechanisms underlining the high clinical variability and resistance but also have characterized H2S as the other active metabolite of this serendipitous drug. To overcome the clinical obstacle of metabolic activation, we have developed the first and stereoselective synthesis of the elusive and unstable active metabolite of clopidogrel. Integrative medicinal chemistry and chemical biology studies have unveiled an intriguing drug action of unprecedented mercapto activation and GPCR protein modification and signaling.

  • Yaoqiu Zhu, PhD
  • University of Texas at El Paso

Yaoqiu obtained his BS in Chemistry in 2001 at Peking University. Under the supervision of Prof. Richard B. Silverman (inventor of Pfizer’s blockbuster drug Lyrica) at Northwestern University, he conducted doctoral studies on enzyme chemistry and got his PhD in 2006. With a strong interest in drug discovery, he joined Abbott/AbbVie as a senior research scientist. He conducted “structure and drug-like property relationship” studies for over 20 internal R&D projects including one that has yielded the HCV drug Viekira Pak. After worked at Abbott for over two years, Yaoqiu resigned and founded his own contract research company, MetabQuest. He independently built a research lab in Beijing, China and had worked with pharmaceutical companies, research institutes and universities on various translational drug discovery projects. To pursue his ultimate career of becoming a professor, beginning 2013, Yaoqiu closed his company and devoted his lab to academic research projects. In the fall of 2015, he started a tenure-track assistant professor position in organic and medicinal chemistry at UT-El Paso.

Hosted by Weiping Tang

To obtain the Webex link for this seminar, contact Debra King at Debra.King@wisc.edu

Date
Friday, October 22, 2021
Time
3:30 PM – 4:30 PM

This event is brought to you by: Pharmaceutical Sciences Division