Looking to the future of Medicinal Chemistry
Posted 3rd November 2017 by Jane Williams
What is the future of medicinal chemistry? Ahead of the executive panel discussion at the upcoming Global Medicinal Chemistry & GPCR Summit, we spoke to David Powell of Inception Sciences Canada about his work and his predictions for the future.
What does a typical day consist of for you?
My role is to do whatever it takes to help advance drug discovery programmes within Inception Sciences. One day, this may mean getting in the lab to help scale up material to support toxicity studies. The next it might mean looking at a potential new target from an academic lab and evaluating the drugability or the quality of the lead molecules identified.
Sometimes it involves diving into the literature to see what information exists that could be used to help us address a hERG problem or a microsomal stability issue. And sometimes it involves listening to team members on another project to see if there is any knowledge I can share to help them succeed. Each day feels very unique, with new questions and problems. It can be challenging at times to proactively organise your week, but it provides the opportunity to really stretch yourself scientifically and learn a ton in the process.
Can you tell us a bit about the work at Inception Sciences?
Inception Sciences is a small molecule drug discovery company, focused on addressing diseases with significant unmet need. We have over 60 researchers working collaboratively across three sites in San Diego, Vancouver and Montreal.
Our projects span a wide range of disease areas, including MS, hearing loss, IBD, ophthalmology and fibrosis. Together with pioneering academic researchers and pharma partners, we are focused on translating breakthrough scientific insights into novel therapies.
One of my favourite aspects of working at Inception Sciences is the expectation for researchers to pay attention to other programmes, participate in cross-site strategy discussion in teams, and offer their input or advice to other teams. It makes for a highly engaging work dynamic, where everyone across the company accepts ownership in advancing the science behind all the programmes, not just their direct project.
What would you predict for the future of medicinal chemistry?
This is a very exciting time to be a medicinal chemist. Drug discovery is going through a continued period of creative destruction. Unlike the tech industry, however, scientific advancements (e.g. PCR, HTS screening, metal-catalyzed cross-couplings, CRISPR-Cas9) usually improve our existing processes rather than transforming our business as a whole. This is expected in a scientific discipline as complex and multi-factorial as drug discovery. Regardless, there are a number of amazing innovations which will likely impact the way we execute medicinal chemistry projects.
There has been a lot of promises regarding the potential of machine learning applied to drug discovery. While I welcome any tools which can help identify novel biology pathways or drug targets, I think a significant impact machine learning will have is in improving the way in which we conduct our day-to-day work as drug hunters.
Application of machine learning to score histological samples from an in vivo study or to evaluate HTS phenotypic screen endpoints can speed up the time it takes to analyse a study, remove researcher biases and possibly increase the quality of the data. I also think there are real applications in medicinal chemistry which haven’t yet been fully realized. Machine-learning could be used to build better QSAR models for physical property, metabolic stability or CYP inhibition profile predictions. It could be used together with the scientific team within a project to identify SAR trends which could feedback in the selection of the next set of compounds to be synthesized by the team. When problems arise (e.g. time-dependent CYP inhibition), machine learning could help scour internal and external databases and propose potential solutions. In concert with a team of experienced medicinal chemists, findings from machine learnings could be applied to multiple facets of medicinal chemistry. Building such tools and interfaces will be a challenge, but the potential benefits could be significant.
Structural biology has provided significant insight into the design of potent and selective molecules. Two recent advancements will likely further increase the role of structure-based drug design in medicinal chemistry. Increased computing power, mainly driven by graphical processing units, is being used to further improve the speed and quality of molecular modelling.
Utilising molecular modelling and molecular dynamics for prioritising new compounds and identifying moieties which contribute to increased ligand-protein binding can help in the design of potent and selective compounds with appropriate physical properties. Combining with the increased power and speed of computational chemistry is an accession in the tools which enable structural biology, most notably, Cryo-EM. The growing application of Cryo-EM to enable high resolution (<3 Å) structural information on ligand-protein interactions, promises to increase the realm and speed of attainable structural information and could provide a more dynamic view of the way ligands bind with proteins.
Finally, as drug discovery becomes more and more challenging, the industry will likely see even greater collaboration across companies. Already the past 10 years have seen pharma companies interact more with academia to remain on the forefront of cutting-edge discoveries.
As we move forward, collaborations across both large and small pharma companies may also expand. This may be appropriate when tackling very challenging diseases (e.g. Alzheimer’s disease), where there is a significant unmet need but high risk. In areas with a finite market opportunity but medical urgency (e.g. anti-bacterial agents), companies may wish to partner on a range of projects. And in disease areas where a combination approach may be most effective (e.g. HBV, NASH, and immuno-oncology), pharmaceutical companies with additive assets may increasingly work together to advance clinical and preclinical programs and ensure significant patient benefit for a given combination treatment. These types of cross-company interactions will require medicinal chemists to think about how they prosecute and collaborate on programmes differently, and will offer new opportunities to learn from one another.
David Powell is Director, Chemistry at Inception Sciences Canada. He will be speaking on the executive panel ‘The Future of Medicinal Chemistry’.
Download the agenda for the Global Medicinal Chemistry & GPCR Summit.
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