Amidst all the advances in scientific understanding and new and increasingly powerful cheminformatics tools and techniques, the perennial question challenging medicinal chemists is “What compound shall I make next?”
Our client is a renowned German pharmaceutical company, focused on human pharma, animal health and biopharmaceutical contract manufacturing with multiple R&D sites worldwide.
The client addresses the pressing what-to-make-next question with a team science approach including medicinal chemistry groups, medicinal chemistry technologies, computational chemistry, and structural research. The simply posed question is difficult to answer because it involves exploring the huge drug-like chemical space, optimizing multiple observed and predicted parameters, and efficiently analyzing and managing massive volumes of disparate data, hypotheses, and workflows. The client wanted to equip its molecular design team with the best digital workflow support tool that could enable rapid and science-driven generation, exploration, selection, and prioritization of potentially promising compounds for synthesis.
Working with Chemaxon during 2018 – 2019, the client co-developed Design Hub, and it is now deployed and used as a central tool by all its compound design teams.
Design Hub emerged from a series of joint client-Chemaxon workshops, discussions, and interviews. A major requirement was to combine all the important compound design and selection tools, techniques, and approaches into a single interactive platform that connects scientific rationale, compound design, and computational resources. These include:
to ensure rational approaches are being used in the design and prioritization of new molecules.
to provide immediate project insights via tools like Kanban Boards on the status, progress, and potential hold-ups of compounds for synthesis and testing.
to capture and potentially reuse compound structure ideas and potential modifications so that no good ideas or insight is lost and can be retrieved, reviewed, and repurposed as needed.
as its name suggests, Design Hub is a central nexus that links multiple data sources and tools required in drug design:
The client’s multidisciplinary compound design teams can also access and use Design Hub in purpose-built design rooms.
These are equipped with touch-enabled large screens or interactive whiteboards with immediate access to all the applications and data sources discussed above. This collaborative environment supports not only prioritization, but work that you would do at your desk - including de novo design, searches, enumerations, property predictions etc. Your new structures can then be characterized and assessed based on synthetic feasibility, predictive models for 3D-protein interactions, and physicochemical and ADMET properties, as well as novelty searches in literature and commercial databases.
The client’s teams use Design Hub for multiple purposes associated with compound design, and a usage survey of designers showed the following very encouraging levels of uptake, with 97% of the respondents using the first four Design Hub activities below frequently or occasionally:
The client also drilled into how individual design teams use Design Hub, comparing their diverse workflows, including organization, meeting preparation, in-meeting, and post-meeting activities. Some teams are open to creating any new hypotheses or design sets, while others limit the number of hypotheses to those based on structural classes or key recurring topics. Another difference was in the handling of links to synthesis planning, where one team transcribed compounds for later discussion, while the other saved the synthesis plans directly in the design set editor in Design Hub and assigned them to lab scientists.
This deeper dive provided several key learnings and pointers to possible platform extensions and enhancements:
The client values the ability to add custom modules to Design Hub, and cited Structural Alerts as a smart assistant that notifies designers in real time that a proposed structure contains a potentially problematic substructure. Others have been deployed, with more to come.
Longer term, the client sees Design Hub as a central tool integrated seamlessly into its digital landscape, and an important part of its best-of-breed strategy. Several interfaces are already established, such as integration with Certara D360 platform, a connection to the compound management system to find and order building blocks, and a smart assistant that makes real-time recommendations from an internal data-driven tool.
Further planned Design Hub connections include the ability to send compounds to an automated retrosynthetic tool, and to a CRO synthesis management tool and receive status updates; and integration with the client’s electronic lab notebook system.
Most significant updates delivered since project start
In summary, facilitating a collaborative and integrated approach, Design Hub empowers scientists with a comprehensive suite of tools, enabling hypothesis-driven drug design, seamless data integration, predictive modeling, and synthesis planning. The platform's flexibility ensures its alignment with evolving research needs and organizational goals. As highlighted by our client's success story, Design Hub not only streamlines workflows but also fosters informed decision-making.