Generate new compound ideas with Nova
Once you’ve identified promising hits, you’ll often need to explore new chemistry to improve key properties. But focusing on a single property in isolation risks introducing liabilities elsewhere.
In this example, we consider three compounds from a lead series and look to improve Serotonin transporter inhibition. We use Nova to generate fresh compound ideas that improve potency while maintaining the balance of other critical properties, reducing potential risk and accelerating optimisation.
Identify new derivatives with Matched Series Analysis
When optimising for target activity, it’s important to understand which chemical substitutions are likely to make a difference. Matched Series Analysis goes beyond Matched Pair Analysis by searching databases of matched molecular series to identify substitutions with a high likelihood of improving binding.
In this example, we use a publicly available set of Human Histamine H1 Ki data to search the ChEMBL pIC50 knowledge base, uncovering new derivatives most likely to improve target activity based on the SAR already generated on the project.
Explore optimisation strategies with Inspyra
When searching for an optimal compound, the sheer scale of chemical space makes it easy to miss the most promising directions. Inspyra works in the background, dynamically learning from your interactions to focus exploration on the strategies most likely to succeed for your specific project.
In this example, we look to identify a selective DPP-4 inhibitor with appropriate physicochemical properties, starting from three chemical series. Follow along to see how Inspyra guides you to relevant chemical space, expanding compound diversity and refining design strategies.
Generate virtual libraries with reaction-based library enumeration
Generating a focused virtual library is a powerful way to systematically explore chemistry around a scaffold, but only if you can quickly home in on the most promising candidates for synthesis.
In this example, we use reaction-based library enumeration in Nova to generate a virtual compound library from pre-defined reagents and well-known reactions, with reagent metadata linked throughout to streamline ordering and synthesis.
Perform scaffold hopping with virtual library enumeration
When a lead series hits a wall, exploring a new scaffold can unlock fresh chemical space, but designing a focused library around it requires balancing structural change with retention of key features.
In this example, we use Nova’s scaffold-based library enumeration tool in combination with R-group analysis to generate a virtual library representing a potential new lead series. We explore the impact of a change of scaffold and variations in a side chain, while retaining the substituents at two key positions.
Getting Support
If you have any questions or need any further support, drop us a line using the form. We look forward to hearing from you!