Review of Efficient Drug Discovery Through Connected Chemistry symposium
Merck Research Laboratories, Boston, was the host for this meeting with a central theme 'Design, Make, Test and Analysis', effecting ...
Information is central to modern drug discovery - each stage of the Design-Make-Test-Analyze cycle generates and consumes large amounts of data in an ever-increasing range of formats. From molecule properties and AI models to CRO synthesis and workload reports you have more information available than ever before.
In Torx we set out to create a platform that provides each user with the information needed to solve today's problem. To do this we envisaged a system that was simple at the point of delivery and dedicated to the task in-hand. The result is a specific set of modules for each stage of the cycle: Design-Make-Test-Analyze.
The initial release of Torx will encompass Design and Make by combining Cresset's expertise in small molecule design solutions (Torx Design) with Elixir's well established chemTraX solution (Torx Make). Test and Analyze modules will follow later in 2020. The result is seamless tracking of small molecules from the inception of an idea, through synthesis, to registration and beyond. At each stage Torx provides you with the information and collaborative environment required to facilitate rapid progression of your project.
Torx Design enables you to gather all the information that you have into a single design centric environment. This could mean presenting important data from predictive models, having a 'live' similarity search to suggest alternative molecules or highlight similar ideas, or a reactive 3D window that provides immediate feedback on the possible interactions with a protein. The key here is flexibility of information display, information source and data type; pictorial and numerical data are handled easily. To do this, Torx Design uses customizable and developable plugins that respond to changes in the design and deliver the information that is available in the format that works best.
Figure 1: Torx Design showing 4 plugins (clockwise from left): My Designs (the molecules that I am personally working on); Editor (for sketching designs, ChemDraw in this case); Viewer (showing the pose of the design within the protein active site); Properties (a table of RDKit properties in this case).
Torx Design presents collaborative as well as design specific information. Designs that have been proposed by colleagues whether internal to your company or in a CRO, can be visualized ahead of any review meeting. Thoughts can be captured through comments, tags or by simply 'liking' a design. Equally designs can be organized together into sets that address specific issues like reducing logD or improving solubility. Finally, as we demonstrated earlier this year, users can join a live shared session to discuss and design together.
Figure 2: Torx Design with 4 alternative plugins (clockwise from left): Review (all the designs that have been proposed by all users in the project); Properties (RDKit properties in this case); Search (molecules and compounds from Torx or other data sources such as ChEMBL or a corporate database); LogP (a pictorial breakdown of the logP contributions generated by RDKit).
In compound synthesis the nature of the information that you need is very different from that in Design with coordination of synthetic resource being of paramount importance. To this end, Torx Make provides an intuitive Kanban style approach that is deeply aware of chemical structures, designs, hypotheses and more. Individual compounds are collated into Design tickets (compounds that taken together address a key question or address a specific issue).
Design tickets can be tracked through the DMTA process, and compounds assigned to individuals or partner organizations, e.g., your CROs, with their synthetic progress reported in real time. Synthetic chemists know exactly which compounds have been assigned to them and team leaders and managers can view progress across all their projects within the organization.
Figure 3: Torx Make showing design tracking. Designs are gathered together according to the problem that they are addressing. Design sets can be prioritized, assigned to individuals or partner companies. Each ticket can contain minimal or verbose information such as proposed retrosynthesis or design hypothesis.
Figure 4: Torx Make showing compound tracking. The customizable view shows exactly which compounds are being made and where. Individual compounds, intermediates or whole design tickets can shared with partner organizations enabling a full view of all synthesis activities in your organization in a single web page.
The Design and Make components of Torx have an underlying workflow that enables you to follow compounds from idea, through synthesis to registration. In Design this is a simple drop down box. Compounds are 'Ideas' until perfected before progressing to 'Review'. This status gathers together all compounds that have been proposed across the project. These designs, together with their physical properties and 3D pose, can be seen by everyone on the project enabling your team to easily view, choose and agree the best compounds to progress.
Once progressed to the 'Agreed' status, designs are transferred to Torx Make for tracking through synthesis to registration. The detailed privacy model in Torx Make means that the synthesis can be in-house or in a partner lab with only the 'need to know' information shared.
Figure 5: A compound in the '5,6 bicyclic core' Design set is advanced from Torx Design to Torx Make where it is progressed to 'In Synthesis'.
Torx is due for release in early 2020. Contact us to register your interest or talk more about how it will accelerate your small molecule DMTA cycle.