Chemical Space Generation

Probably the most important unique selling point of individual Chemical Spaces is their uniqueness.

• By setting up your own compound collection, you create a proprietary chemical universe.
• Studies have reported that overlap among Chemical Spaces is minimal, meaning that each Space contributes access to additional, unique chemical regions.
• Any emerging chemotypes are more likely to be truly novel. This is especially valuable for:
  • Patenting
  • Partnering
  • Attracting investors

The content of Chemical Spaces is synthetically realistic.

• Only one or two-step chemistry is required to realize products, contributing to high synthesis success rates.
• Retrieved chemistry can be novel while avoid the problems of de novo design (e.g., exotic, impractical, or even impossible to make).
• Chemotypes can be creative, but are grounded in real chemistry.

Not only do they feature several orders of magnitude more compounds than old-fashioned compound catalogs, but can be screened even faster.

• Billions or even trillions and more can be achieved with a custom Space.
• Several 2D and 3D methods are available to explore the Chemical Spaces smarter without wasting many computational resources.
• Unexpected chemotypes can still be discovered without relying on brute-force docking or blind screening.
• A custom Chemical Space comes with originality and control.

Your ultra-large virtual compound collection can grow with the needs of the projects and be adapted.

• The initial version of your Chemical Space can be refined based on a run cycle of a campaign.
  • Add new building blocks to expand the possibilities around discovered actives.
  • Remove unproductive reagents and reactions to improve success rates.
  • Adjust reaction schemes.
• The DMTA (design, make, test, analyze) cycle is accelerated with the Space technology as an engine for making more informed decision and improved access to relevant structures.
• Over time, your Space becomes more optimized and efficient for your specific drug discovery challenges.

While generic compound collections try to provide a broad chemical coverage, your Chemical Space can be designed to provide custom solutions to your target.

• Employing specific building blocks and reactions leads to population of scaffold areas that display pharmacological activity at your target.
• Chemical Spaces provide more related compound to a compound of interest and have a broader chemical coverage compared to enumerated libraries.
• Undesired chemistry can explicitly be excluded (e.g., structures responsible for toxicity, off-target effects, solubility issues).
• Chemical Spaces can be mined for molecules to create custom sublibraries.

Creating a Chemical Space is surprisingly simple: you need building blocks (compounds with functionalizable groups) and reactions (rules for how to combine them).
In advance, you should not worry too much about the number of building blocks or reactions. Due to combinatorics, even a small number of simple reactions already leads to exponential generation of products. Thus, even just a few thousand building blocks can open up trillions of possibilities.

Reactions can be derived from common databases. Alternatively, our Cookbook offers a selection of proven and robust reactions that can be used as a starting point for further extensions and adaptations.

The generation of the Chemical Space file (.space) is achieved with our tool CoLibri.

Medicinal chemists are central to realizing the full value of a Chemical Space, since they can interpret it and guide its evolution.

• They can:
  • Cherry-pick building blocks to increase the chemical diversity or to cover desired scaffolds.
  • Encode their intuition into the Space design via reaction schemes.
  • Assess the quality of retrieved results.
• The contribution makes the process more interpretable, more collaborative, and elevates the results beyond the scopes of de novo generated proposals.

Setting up your own Chemical Space comes with strategic advantages that make you more flexible and efficient.

• Embedding a Chemical Space into your workflow enables you to concentrate your limited resources on the most high-value regions of chemistry.
• Time and cost are conserved by minimizing the synthesis of low-priority or irrelevant compounds.
• Higher-quality hits can be identified more rapidly, enabling faster progress and earlier insights.