June 13 2022
The "Joint Invited Speaker Seminar Series for Future Medicine" will be co-hosted by Korea Advanced Institute of Science and Technology (KAIST) GSMSE and International Research Center for Medical Sciences (IRCMS). It will run from May 2022 to September 2022, with lecture given by scientists who are affiliated with IRCMS or in collaboration with reseachers at IRCMS. The lectures will be given three times a month, in English, and by leading scientists in the relevant research field.
Date : June 29th (Wed)
Time : 10:00 (JST)
Speaker : Dr. Wonhwa Cho
Department of Chemistry, University of Illinois Chicago, U.S.A.
Title : Development of resistance-proof cancer drugs
Small molecule inhibitors for kinases are the mainstay of targeted cancer therapy but drug resistance remains a major problem in conventional kinase inhibitor development. To overcome this challenge, we developed a new strategy of targeting lipid-protein interaction that is essential for cellular functions of numerous non-receptor kinases. Our pilot study focused on non-receptor kinases containing the Src homology 2 (SH2) domain, based on recent studies showing that membrane lipids control both catalytic and non-catalytic scaffolding activity of these kinases via lipid-SH2 domain interaction. Through advanced computational analysis and construction and screening of a new chemical library, we developed novel small molecule inhibitors of the lipid-SH2 domain interaction that potently and specifically block the cellular activity of their host proteins. Spleen tyrosine kinase (Syk) is a SH2 domain-containing signaling protein implicated in multiple hematopoietic malignancies, including acute myeloid leukemia (AML). A lipid-Syk-SH2 interaction inhibitor (WC36) suppressed oncogenic signaling activities of Syk in various AML cells, including patient-derived AML cells, more specifically and potently than available Syk inhibitors. Most importantly, WC36 was refractory to de novo and acquired drug resistance that renders conventional ATP-competitive Syk inhibitors ineffective. This exceptional activity of WC36 derives from its ability to efficiently block both the kinase activity and kinase-independent scaffolding function of Syk, the latter of which is linked to the drug resistance mechanism. Given that lipids play similar critical roles for numerous non-receptor kinases, this new strategy of targeting drug resistance at the source should aid in development of a new class of resistance-proof drugs. Collectively, our study serves as a proof of concept that targeting lipid-protein interaction is a powerful new approach to novel drug discovery.
This seminar will be held via Zoom.
Please register at the link below if you would like to participate.https://docs.google.com/forms/d/e/1FAIpQLSenZyyWw2h4XA4GhJUwaoMbZb95CNstqAFWcWkHiN451rDwMg/viewform?usp=sf_link