Chemical diversity and an included “uniqueness” are the main features of every Chemical Space. The REAL Space from our friends at Enamine is widespread and of high renown in this regard. In the latest February 2022 Update, the REAL Space underwent another huge expansion leading to a stunning number of over 23 billion commercially available compounds that can be synthesized and delivered to customers within only a few weeks. The addition of approximately two billion novel compounds further increases the chemical diversity of the Chemical Space and it is now even more likely to contain interesting compounds for your drug discovery projects.. In a recent post we highlighted the importance and the potential of every individual Chemical Space due to the small overlap of entries featured in them.
In the example below we show a search with our infiniSee software across the REAL Space. Belumosudil, an inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2) which received FDA approval for the treatment of chronic graft versus host disease in 2021, was used as query compound with different search parameters to investigate the chemical diversity of potentially related compounds.
Users can control the outcomes of infiniSee searches by applying different search parameters. Focusing on high similarity between query and result compounds (e.g., using standard parameters) returns compounds that share a close resemblance to the query. In general, these results share molecular features and can be close analogs to the query molecule. This approach can be appropriate if you desire compounds with similar pharmacophore features yet lie in close chemical proximity to the query.
Increasing the chemical diversity setting returns entries with higher variety among themselves that are still related to the query molecule. This method is perfectly suited for investigating compounds with respect to scaffold hopping and exploring the possibilities within the Space itself.
If particular molecular features are important, users can apply constraints on functionalities. These constraints will be considered during the search and will be present in the results. This makes it is possible to retain a key feature of the drug (e.g., a hinge-binding motif) and focus on a particular area of the Chemical Space.
Did this get you excited about discovering accessible molecules for your target? Download the REAL Space Update featured in the most recent version of the Chemical Space Nagivation Platform infiniSee, and start drug hunting today!