Virtual Meeting of the Princeton ACS Section http://chemists.princeton.edu/pacs/event/pacs-virtual-meeting-july-15/
Wednesday, July 15, 2020, 11:30 AM “GoToMeeting”
Colin Suckling, PhD
Research Professor of Chemistry, Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, Scotland
“Off Paradigm Drug Discovery and the AMR / COVID-19 Era”
Abstract- For many years it had been recognized that the world was facing a problem in the lack of new anti-infective drugs to tackle the increasing prevalence of microbial resistance to existing drugs. The global pharmaceutical industry had largely ignored the problem for understandable commercial reasons. The standard industry drug-discovery paradigm of single drug, single target leading to predefined beneficial effect also imposes limitations on the discovery of resilient antimicrobial drugs because resistance can easily arise from mutations in the target (together with other mechanisms). Such target driven drug discovery is powerful but in fields such as anti-infective drugs, other approaches that I call ‘off-paradigm’ become highly relevant if they lead to resilient new drugs. This was the approach we took at Strathclyde using minor groove binders for DNA (S-MGBs) and we have been able to discover a wide range of anti-infective compounds for bacterial, fungal, and parasitic diseases, the most advanced of which has successfully completed a Phase 2a clinical trial.
Then along came COVID-19 and changed the world. Interestingly and perhaps surprisingly some of our S-MGBs had shown high activity against hepatitis C virus in vitro. This raised the obvious question of whether S-MGBs would be active against COVID-19, a question that is being addressed right now. Further, the acute effects of COVID-19 infection including the so-called cytokine charge and serious lung disorders pointed to the importance of another of our off-paradigm drug discovery projects in the field of anti-inflammatory and immunomodulatory compounds. In this second project, from the starting point of a protein secreted by a parasitic nematode worm we discovered a range of compounds, known as SMAs, that have been shown to be highly effective in a wide range of animal models of disease, including some relevant to treating COVID-19 patients. This talk will discuss the design, biological activity, and mechanism of action (as much as is known) of S-MGBs and SMAs and speculate about their potential contribution to treatments for COVID-19 infections and future biosecurity.
Biography - Colin Suckling is a graduate of the University of Liverpool (BSc 1967, PhD 1970, DSc 1989) and has spent most of the rest of his academic career at the University of Strathclyde where he was Freeland Professor of Chemistry from 1989 to 2012. During the 1990s until 2002, was Dean of the Faculty of Science, Deputy Principal, and Vice Principal of the University. Currently he is a Research Professor of Chemistry.
Research interests focus on the synthesis and properties of heterocyclic compounds designed as molecular probes for biological systems and as drugs for treating infectious and inflammatory diseases. The most advanced compound, a DNA Minor Groove Binder (MGB), has successfully completed a phase 2a clinical trial for the treatment of Clostridium difficile infections (May 2020). Other compounds in the Strathclyde collection of MGBs are nearing candidate selection status as treatments for African Animal Trypanosomiasis and also as antifungal compounds. A further advanced project in medicinal chemistry entering the commercial phase concerns immunomodulatory compounds based upon the structures of protein secretions of parasitic worms. The small molecule analogues of the parasite protein show great promise as treatments for inflammatory diseases such as rheumatoid arthritis, asthma, and lupus.
Colin has published over 250 papers and books. He was the Adrien Albert Lecturer of the Royal Society of Chemistry (2009-10), Chairman of the 2011 International Congress of Heterocyclic Chemistry held in Glasgow, recipient of the Nexxus Lifetime Achievement Award (2011), and elected an Honorary Life Fellow of the Indian Society of Chemists and Biologists (2011). Colin is a Fellow of many learned societies and Royal Colleges including the Royal Society of Chemistry, the Royal Society of Edinburgh, the Royal College of Surgeons of Edinburgh and the Royal College of Physicians and Surgeons of Glasgow. He was a B.D Tilak Fellow of the Indian Institute of Technology, Mumbai, in 2019.
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