Dual targeting compounds and PROTACs – exploring the unique pharmacological challenges of bifunctional molecules

Venue: CeTPD Seminar Room

Abstract:

As drug discovery scientists look for more effective therapeutic strategies to treat disease, dual targeting inhibitors and PROTAC molecules are emerging as powerful agents that can overcome limitations of conventional single target agents. These classes of bifunctional molecules also carry new challenges for chemists and pharmacologists as they typically stray beyond conventional SAR and the historic “rules” for compound development.

In this presentation, case studies in an anti-cancer drug discovery (Dual inhibitors of BET/PI3K) and anti-viral drug discovery (MPro PROTACs for SARS CoV-2) from our group will be used to highlight successful and not-so-successful examples of bifunctional compound development.

References:

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Oh, D. H.; Ma, X.; Hogg, S. J.; He, J.; Kearney, C.; Brasacchio, D.; Susanto, O.; Maher, B.; Jennings, I. G.; Newbold, A.; Fraser, P.; Gruber, E.; Kats, L. M.; Gregory, G. P.; Johnstone, R. W.; Thompson, P. E.; Shortt, J. Rationally designed chimeric PI3K-BET bromodomain inhibitors elicit curative responses in MYC-driven lymphoma. Proc Natl Acad Sci U S A 2023, 120, e2306414120.