【北京大学无机化学学术论坛】Texas-inspired Drug Discovery Efforts

 

报告摘要

This lecture will present the development of expanded porphyrins--larger analogues of heme pigments--as a class of compounds and as potential drug leads. The presentation will center around my personal story of a 3x cancer survivor and how with the assistance of great coworkers and collaborators an effort has been made to fight back against this disease by studying the chemistry and anti-cancer biology of gadolinium(III) texaphyrins. Texaphyrins were the first of the so-called expanded porphyrins to stabilize a 1:1 complex with a metal cation. Subsequently, effort was made in our laboratories and those of many others to create additional expanded porphyrins. Hundreds are now known. Several from our laboratory show promise in biomedical applications. Recently, efforts have been made to create so-called immunogenic cell death promoters designed to prevent cancer recurrence based on redox-active gold(I) carbenes. This new line of research will be reviewed as time permits.

Collaborations with a number of groups, including those of Profs. Dongho Kim, Andrew Gaunt, John Arnold, Stosh Kozimer, Jong Sung Kim, Shunichi Fukuzumi, T.K. Chandrashekar, Dirk Guldi, Changhee Lee, Jan Jeppesen, Steffen Bähring, Zahid Siddik, Rick Finch, Zhengrong Cui, Jingqin Chen, Dani Gibson, Zhao-Xi Wang, Aaron Tondreau, Chuanhu Lei, Hongyu Wang, Jun-long Zhang, and Tomas Torres, are gratefully acknowledged. Special thanks also go to former coworkers, including Han-Yuan Gong, Jonathan F. Arambula, Gregory Thiabaud, Sajal Sen, Qing He, Zhan Zhang, Xian-sheng Ke, Xiaofan Ji, Xiaodong Chi, Atanu Jana, Adam Sedgwick, James Brewster, Jungsu Park, and Daniel Mangel. Support for this work is being provided by the National Science Foundation and the Robert A. Welch Foundation.

Keywords: expanded porphyrins; texaphyrins; cancer; ICD; gold carbenes

References

  1. J. L. Sessler, T. Murai, V. Lynch, and M. Cyr, J. Am. Chem. Soc., 1988, 110, 5586.
  2. G. Thiabaud, G. He, S, Sen, K. A. Shelton, W. B. Baze, L. Segura, J. Alaniz, R. M. Macias, G. Lyness, A. B. Watts, H. M. Kim, H. Lee, M. Y. Cho, K. S. Hong, R. Finch Z. H. Siddik, J. F. Arambula, and J. L. Sessler, Proc. Natl. Acad. Sci. USA, 2020 117, 7021.
  3. S. Sen, S. Hufnagel, E. Y. Maier, I. Aguilar, S. Jayaraman, J. E. DeVore, V. M. Lynch, K. Aramugam, Z. Cui, J. L. Sessler, and J. F. Arambula, J. Am. Chem. Soc., 2020, 142, 20536.
  4. J. Chen, A. C. Sedgwick, S. Sen, Y. Ren, Q. Sun, C. Chau, J. F. Arambula, T. Sarma, L. Song, J. L. Sessler, and C. Liu, Chem. Sci., 2021, 12, 9916.
  5. Kim, J.; He, H.; Lee, Y. J.; Zong, Z.; Liu, N.; Lynch, V. M.; Oh, J.; Kim, D.; Sessler, J. L.; Ke, X.-S. J. Am. Chem. Soc., 2024, 146, 543.

报告人简介

Prof. Jonathan L. Sessler was born in Urbana, Illinois, USA on May 20, 1956. He received a B.S. degree (with Highest Honors) in chemistry in 1977 from the University of California, Berkeley. He obtained a Ph.D. in organic chemistry from Stanford University in 1982 (supervisor: Professor James P. Collman). He was a NSF-CNRS and NSF-NATO Postdoctoral Fellow with Professor Jean-Marie Lehn at L’Université Louis Pasteur de Strasbourg, France. He was then a JSPS Visiting Scientist in Professor Tabushi’s group in Kyoto, Japan. In September, 1984 he accepted a position as Assistant Professor of Chemistry at the University of Texas at Austin, where he is currently the Doherty-Welch Chair. Dr. Sessler has authored or coauthored over 900 research publications (including over 200 in the J. Am. Chem. Soc.), written two books (with Dr. Steven J. Weghorn and Drs. Philip A. Gale and Won-Seob Cho, respectively), edited two others (with Drs. Susan Doctrow, Tom McMurry, and Stephen J. Lippard, Placido Neri and Mei-Xiang Wang), and been an inventor of record on over 90 issued U.S. Patents. Dr. Sessler was a co-founder (with Dr. Richard A. Miller) of Pharmacyclics, Inc., which was acquired by AbbVie for $21B in 2015. His texaphyrin technology is now the basis for a new company, InnovoTex, Inc. In addition to English, Dr. Sessler speaks French reasonably well, as well as Hebrew and Spanish. He also knows a little bit of German and Japanese, and a couple words of Korean. Dr. Sessler’s work has been recognized with several awards, including the American Chemical Society Cope Scholar and Breslow Awards, the Royal Society of Chemistry Centenary Prize, as well as Mond-Nyholm and MASC Supramolecular Chemistry awards, the Molecular Sensors-Molecular Logic Gates Award, the CASE award, the Hans Fischer and Thomas Dougherty Awards in Photodynamic Therapy from the Society of Porphyrins and Phthalocyanines, and the C. David Gutsche Award in Calixarene Chemistry. Dr. Sessler is a member of the U.S. National Academy of Inventors, the European Academy of Sciences, the U.S. National Academy of Sciences, the American Academy of Arts and Sciences, and the Chinese Academy of Sciences (Foreign Member). He has been a Clarivate Highly Cited Researcher for many years.

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