March 2021 newsletter
Case study: Investigating the SAR of RIPK1 inhibitors Understanding SAR is fundamental in many aspects of drug discovery, from exploring ...
I think it’s fair to say that 2020 will not go down in most people’s memory as a ‘classic’, but it’s bound to be a year that we remember, even if the events we recall are not all positive. However, despite the issues and the worries brought about by the global pandemic, there have also been lots of reasons to celebrate the year and the enjoyable moments we have had. If anything, I think the pandemic has made me even more sharply aware of the privilege of having a lovely family and a job which I enjoy in a company which has thrived despite the external challenges.
The first significant change for us this year is that, just after I wrote my 2019 end of year message in December last year I then had the unhappy task of reporting the news that Andy Vinter had passed away. Those of us who had the good fortune to work with Andy miss him hugely. Understandably, our memorial to Andy had to be delayed this year due to the coronavirus pandemic, however we are planning a tribute to his work at our User Group Meeting in 2022.
One of the most noticeable changes through the year has been the disruption to travel plans, customer visits and conferences, plus more locally, the necessity for the majority of us to work from home. We had to rapidly change our approach to interactions, both internal and external, adapting to the ‘new normal’. I extend my thanks to the Cresset team for their hard work dedication during this time.
The Cresset team has seen continued growth world-wide this year, with new colleagues in most areas, including computational chemistry development, application science, project management, account management, QA, web development, marketing and HR. This growth, on the back of that seen in previous years, has seen the team double in number in the last three years.
As well as our Cresset team, I’m grateful to the support we receive from our distributors. Through this network customers continue to access our solutions in China, India, Japan and South Korea. This year, we have welcomed 4am Software to the fold who will ensure research chemists in Australia and New Zealand benefit from Cresset technology.
An important step for our future development, as we expand the capabilities of our scientific software offering, is the launch this year of our Scientific Advisory Board, chaired by Dr Stevan W Djuric, a widely respected scientist with a strong track record of success in both medicinal chemistry and in the application of novel technologies to increasing the power and efficiency of the drug discovery process. The SAB will help guide the development of the next generation of tools to accelerate product discovery cycle times and success rates at a time when the industry is encountering more and more diverse and challenging targets.
As FEP gains in popularity, our paper Assessment of Binding Affinity via Alchemical Free Energy Calculations J. Chem. Inf. Model. 2020 demonstrates that, when correctly executed, FEP can accurately calculate the relative binding energy of a closely related series of ligands. Through our collaboration with the University of Edinburgh we are improving the speed and efficiency of our FEP offering, with multiple enhancements planned over the next few releases of Flare. To enhance our structure-based platform capabilities we’ve joined the Open Force Field Consortium; as part of this collaboration we will work with industry and academia to develop a new force field for small molecules.
As alluded to above, a significant highlight this year was the introduction of FEP in Flare™, our structure-based design platform. This new functionality enables research chemists to accurately predict compound activity in lead optimization projects, saving time and reducing the cost of additional resource required for synthesis by accurately prioritizing the best molecules.
Spark™, our bioisostere and scaffold hopping solution, has recently been updated to version 10.6. Computational and medicinal chemists can now explore new chemical space through new and improved search methods to generate innovative ideas for their drug discovery projects. The new docking feature enables them to find novel results making protein-ligand interactions not present in the reference molecule. Additionally, the Spark fragment and reagent databases have been updated. Customers tell us that Spark is the best bioisostere tool they have used, so I was delighted to read Dave Evans and Matthew Baumgartner’s paper ‘Side chain virtual screening of matched molecular pairs: a PDB-wide and ChEMBL-wide analysis’ in J Comput Aided Mol Des (2020). Mark Mackey’s summary of this paper provides a fascinating new take on evaluating methods for finding bioisosteres.
A key feature of the year for us all at Cresset is our annual User Group Meeting. We were all as disappointed as those who were planning to present and attend when we had to change to a virtual format. Although we missed the opportunity to meet with you face-to-face, I was delighted with the online attendance and will build plans into future meetings to deliver online content alongside the physical meeting. Presentations from this year are online, and we will keep you informed of plans for the 2021 User Group Meeting as they develop.
The webinar series Advancing your drug discovery pipeline kicked-off in October and continues into next year. The webinars held to-date have explored the rapid generation of ideas for novel molecule cores and chemical series, and the pre-requisites for ensuring a successful FEP simulation using Flare™ to prioritize the best compounds for synthesis. If you missed these webinars but would like to receive a recording contact your account manager. I hope you’re able to join us for upcoming webinars where you will learn how to exploit project knowledge to inform ligand design, how to find new leads from peptides and natural ligands and how to streamline the design of covalent inhibitors.
Over the last year we have seen an increasing demand from companies looking to add to their existing computational chemistry capabilities, outsourcing research projects and submitting grant applications. As a result, we’ve expanded the team and now have dedicated project and account managers so our scientists can be absolutely focused on customer project work.
Our team of Cresset Discovery Services CADD scientists continue to deliver a wide range of services. Due to confidentiality, we unfortunately cannot talk about most of this work, however you can read about some of the projects we’ve worked on for Liverpool ChiroChem, ZEAB Therapeutics and InoCardia.
Following the launch of FEP in Flare earlier this year, we’ve also seen an increasing demand from customers looking to outsource FEP projects. Customers may lack the in-house expertise to successfully set up and run the complex calculations required by the method or they may not have access to the scale of high-performance computing required to execute the calculations in reasonable time. The Cresset Discovery Services team are excited to work on these projects to help customers increase the efficiency of their drug discovery projects.
Two years ago we announced a project to deliver a web-based platform for small molecule discovery chemistry, through our partnership with Elixir Software. I am delighted to say that the first fruits of the collaboration, Torx™, was launched this year. This turned out to be very timely, due to COVID-19 which has impacted considerably the way research teams are working this year, Torx re-imagines the scientific workflow, capturing all information throughout the Design-Make-Test-Analyze cycle. Those who attended our recent webinar will have learnt how Torx Make™ eases the ability to know the status of every project compound, in seconds. I hope you’re able to join us at the upcoming webinar which explores the use of Torx Design™ to create new molecules, share ideas with others in the project and collaborate in real-time.
With InoCardia we are developing improved computational methods for cardiac safety assessment in a collaboration which also includes the University of Coventry and UCB and is supported by EIT Digital. By using in silico predictions we aim to reduce the number of time-consuming and expensive wet biological assays required to develop better and safer treatments.
Last year we announced a partnership with Liverpool ChiroChem. Cresset Discovery Services were contracted to analyze and select an optimal set of scaffolds and reagents in order to build a virtual library of readily accessible product molecules. LCC’s video describes the project and our joint approach to large scale library design.
With the goal of accelerating development of therapeutic interventions for oncology and ophthalmology, we have been partners in the 3D-NEONET consortium. We welcomed PhD students from University College Dublin who used Cresset technology to analyze protein targets, build homology models, run virtual screens and analyze the results. The skills the developed working with us will enable them to address key challenges facing research and innovation today.
This year we continued to support our colleagues who have links to community or charitable initiatives through our corporate social responsibility initiative. Cambourne United under 7s football team and Holmes Chapel RUFC have both been sporting kit sponsored by Cresset. Additionally, we provided Sands, the stillbirth and neonatal death charity, with a digital camera for use by their bereavement team at the Rosie Maternity Hospital in Cambridge. UK.
Although this year has been challenging, I am proud of how passionately each member of our team contributes both individually, and through their team working to ensure our many customers have access to the most powerful, innovative and intuitive software and services.
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I wish all our customers, partners and colleagues and peaceful and prosperous 2021. I hope to have the opportunity to meet with many of you in the coming year.