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CoLibri: use cases

no active site – where do I start?

If you are working on a GPCR project (or any other project lacking a protein structure) and cannot follow the traditional structure-based design approach, mining a virtual chemical space will be a useful approach to generate inspiring new chemistries as starting points.
Boehringer-Ingelheim used this approach to propel a GPR119 project. They started out with 4 structurally different literature compounds as queries to search their in-house virtual, BI-CLAIM to generate 10,000 FTrees hits. These were post-processed by a 3D shape filter based on one of the more rigid query compounds. Specific cores of the molecules were selected by the chemistry team as "activity anchors" and focused libraries around these designed and synthesized.
This approach lead to two new GPR119-agonist hit series, one of which subsequently resulted in a new lead class. Read more details in the original publication:

Identification of New Potent GPR119 Agonists by Combining Virtual Screening and Combinatorial Chemistry
B. Wellenzohn, U. Lessel, A. Beller, T. Isambert, C. Hoenke, and B. Nosse
J. Med. Chem., 2012, 55 (24), pp 11031-11041

how to increase the IP-value of my space?

KnowledgeSpace™ is freely available chemical space covering hundreds of billions of virtual products. It can be searched out of the box, but being based on literature reaction protocols and commercially available reagents its IP-value is low. However, since we provide not only the space but also the reactions and the entire workflow to generate it, you may use this as a blueprint and design your own space using KnowledgeSpace™ as a jump-start. You can easily raise the IP-value by augmenting the space with your own proprietary reaction protocols and also by using your in-house building block collection.
Evotec did that. They used the KnowledgeSpace™ as a foundation and added their collection of 36 Mio in-house compounds (EVOsource) and several in-house reactions. The resulting virtual chemical space EVOspace comprises hundreds of billions of virtual products.

Just in KNIME: Successful Process Driven Drug Discovery
M. Mazanetz
KNIME® Spring Summit, Berlin, Germany, Feb. 2016

can I create my own chemical space?

Many companies have a unique collection of in-house chemistries and building blocks, and therefore want to set up their own space, based on those in-house chemistries and building blocks. This will also create the highest level of IP-value. Pfizer did that and built PGVL. They turned 358 combinatorial libraries based in validated reaction protocols into a virtual chemical space, resulting in 3 trillion chemically accessible compounds. Read more in the original publication:

Similarity Searching and Scaffold Hopping in Synthetically Accessible Combinatorial Chemistry Spaces
M. Boehm, T.-Y. Wu, H. Claussen and C. Lemmen
J. Med. Chem., 2008, 51 (8), pp 2468-2480

I feel lucky

Sometimes you may reach a point in your project at which you just want to see what's possible. In such a scenario, you could use one of our KNIME® or Pipeline Pilot® nodes.

  • Draw a structure from scratch, and use that as a query to search a fragment space (be it the KnowledgeSpace™ or your own). Filter the resulting molecules with KNIME®'s or Pipeline Pilot®'s powerful filtering functions, generate the 3D structures of the molecules, use a shape filter or dock them into an active site using LeadIT/FlexX and then estimate the affinity with SeeSAR, all in one convenient workflow. This is the approach we took in our BioSphere workflow.
  • Alternatively try growing your lead using our popular STORM workflow. This is a pocket explorer that follows a certain reaction vector and finds the most promising and synthetically accessible virtual hits.
  • Finally MedChemWizard does all sorts of med-chem transformations to a given molecule. Use it to find a magic methyl, do a nitro-walk around rings, find ring-analogs and other bio-isosters. MedChemWizard tries it all, does the virtual validation, and conveniently provides you with the most promising suggestiones for visual inspection.

none of the above...

Don't see your case reflected here, or have a drug discovery problem you need a solution for? We can help

  • putting together a workflow for you to adequately address your challenge
  • employ the most advanced computational drug discovery technology for you
  • design your proprietary chemical space
  • find hits and evolve them into lead structures
  • collaborate with the best-in-field to provide and end-to-end solution

Simply contact our service team and ask for a free assessment.


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