Reviewing the Global Medicinal Chemistry and GPCR Summit
Posted 29th January 2018 by Laura Berry
MedChemNet and Future Medicinal Chemistry were thrilled to attend the Global Medicinal Chemistry and GPCR Summit, organised by Global Engage. The event shared the latest in medicinal chemistry and GPCR developments with delegates from across the globe. Represented at the summit were a number of large and small pharmaceutical companies, as well as biotechnology companies, CROs and academics.
Following breakfast and ample time to network, the first keynote address was given by Emma Parmee (Merck, Sharpe & Dohme (MSD), NJ, USA). Parmee provided an insight into the latest drug discovery developments at MSD, describing their efforts to develop new technologies to allow high throughput experimentation in small amounts, before these compounds are used directly in biology assays. This should help to find more drug hits and increase the speed of the drug discovery process.
After a break, the day split into three tracks, focusing on enabling technologies, medicinal chemistry strategies and G-protein coupled receptors. We chose to attend the talks on enabling technologies and medicinal chemistry strategies, as we were really interested in finding out about a variety of up-and-coming drug discovery technologies.
To start this off, we listened to David Wilson (AstraZeneca, Cambridge, UK) deliver a talk on the discovery of AZD5991, a potent and selective inhibitor of Mcl-1 and a key protein implicated in oncology. He described the latest research at AstraZeneca into drugging protein-protein interactions and how macrocyclisation can be utilised successfully in lead optimisation, shown in the development of AZD5991 – a drug that has caused complete tumour regression in mouse models.
Andreas Brunschweiger (TU Dortmund, Germany) presented his lab’s work on accessing genetically tagged heterocycle libraries via a chemoresistant DNA sequence, highlighting the use of DELs in drug research. They are researching the use of hexathymidine sequences in the initial step of DEL synthesis, in order to remove the bias from the chemical space of DELs that arises as it is only possible to utilise DNA-compatible synthesis methods.
In track two, Sam Mann (Charles River, MA, USA) described their recently acquired capture compound mass spectrometry technology and its use in drug discovery. This exciting technology allows unbiased identification of protein targets for small molecules, and is superior to classic affinity pull-down as it can bind proteins with very low affinity and be used to identify extra- and intra-cellular targets on living cells.
After more snacks, and plenty more time to meet other delegates and view the posters and exhibition stands, the final three talks I attended were on the topic of proteolysis targeting chimeras (PROTACs) delivered by Ian Churcher (BenevelentBio, London, UK), George Burslem (Yale University, CT, USA) and Alessio Ciulli (University of Dundee, UK). These talks highlighted the recent research by multiple institutions into the degradation of proteins as a therapeutic strategy and the benefits of protein degradation compared with inhibition. PROTACs are an exciting and emerging topic in medicinal chemistry, and involve the utilisation of small molecule linkers to bind both E3 ubiquitin ligases and the target protein for degradation, causing polyubiquitylation of the target protein, and its consequent degradation by the proteasome. Could this technology be the future of drug design?
The next Medicinal Chemistry Summit will take place September 17 – 18 in Boston. Take a look at the agenda.
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