On Wednesday 14th March 2018 I attended the RSC Biomedical and Medicinal Chemistry Sector’s 4th Mastering MedChem Symposium. The opening session chair, Professor Joe Sweeney (University of Lancaster) described the event as the sector’s “most successful new conference”. This year it was being held at my almer mater, University of Strathclyde in Glasgow.
The day was split into three sessions where a series of talks from a mixture of speakers across academia and industry shared stories of good practice in drug discovery. A variety of disease areas were covered. Prof. Stuart Conway (University of Oxford) gave a useful overview of epigenetics and bromodomain ligands. Malaria was covered by Prof. Ian Gilbert of the University of Dundee’s Drug Discovery Unit, although I was surprised to learn the project had progressed as far as it had given no mode of action for their compounds had been elucidated due to the complex nature of the malaria disease pathway.
During the lunchbreak and afternoon coffee session I was able to chat to attendees about the poster I had brought which summarised some of my PhD project involving the development of kinase inhibitors to target cancer via a synthetic lethality strategy. It was interesting discussing with other students attending with posters how they had prepared similar benzimidazole compounds to mine but for entirely different disease targets.
While I was a tad concerned there would be no conversation around kinases given the general nature of a number of the talk titles, Dr. Iain Simpson of AstraZeneca shared the story of the optimisation of a compound for a kinase project that, serendipitously, had the same core as one of my own series. It was very useful to speak to him afterwards to compare notes on dialling in selectivity for our respective targets.
There were also more generic talks about the industry and techniques for improving the efficiency of the laborious drug discovery process. Prof. Adam Nelson (University of Leeds) commented on the small pool of reactions most medicinal chemists use for preparing libraries (amide formation, Pd-catalysed couplings, alkylations etc.). He also shared a way of finding bioactive compounds faster without having to purify every single reaction run in the lab by assaying crude reaction mixtures and then only scaling up and purifying reactions with bioactive components, which he termed “activity-directed synthesis”, a rather intriguing method but must have limitations given the toxicity of many chemical reagents!
Dr. Craig Johnstone (Evotec) gave examples of case studies where focussing on multiple drug parameters at once had increased the productivity of a number of his company’s projects, instead of the scenic route most projects take to optimise individual physiochemical properties. He spoke about the potential of artificial intelligence to predict what reactions would work before heading into the lab and he also took an opportunity to justify his theory that every good drug candidate has a logD of around 2.
To round up the day, the memoriam McGuigan Lecture was given by Prof. Chris Schofield (University of Oxford) who took us on a whistle-stop tour of the development of inhibitors of serine and Zn(II) dependent beta-lactamases and their involvement in combating bacterial resistance. Due to the unfortunate absence of Dr. Nicole Hamblin from Charles River laboratories (the only female speaker in the programme I might add), an alternative Q&A was held with a panel of the speakers from the day. Attendees asked a number of questions around the feasibility of artificial intelligence in drug discovery, the importance of specialisation for career progression and a particularly useful discussion point in their careers often have to keep moving around the country, jumping from project to project, before a rare long-term lectureship or industry post arises, if at all. The panel sympathised with this view and mainly came to the conclusion that the way research is funded needs to change to give scientists more sustainable livelihoods.
I found the symposium to be a very useful experience, particularly as it was aimed at early career researchers such as myself. It was nice to be back in Scotland for a bit and I would hope to attend future Mastering MedChem meetings.
Blog written by Fiona Scott, PhD researcher, Sussex Drug Discovery Centre