The IMS Library: from IN-Stock to Virtual.

Area of Science:

• Medicinal Chemistry
• Chemoinformatics
• Drug Discovery

Background:

• Chemical library design is crucial for early-stage pharmaceutical research, influencing drug discovery success.
• Optimizing library size, diversity, and synthetic accessibility is key for cost-effective research, especially in academia.

Purpose of the Study:

• To propose chemoinformatics methodologies for tailoring chemical libraries.
• To create a diverse panel of under 1000 compounds from a larger pool.
• To expand pharmacophoric diversity using a virtual chemical library.

Main Methods:

• Analysis of an initial 10,000-compound pool using chemoinformatics tools.
• Development of two tailored libraries: eIMS (in-stock compounds) and vIMS (virtual compounds).
• vIMS creation involved adding functional groups to eIMS scaffolds and filtering for synthetic accessibility and drug-like properties.

Main Results:

• The eIMS Library contains 578 diverse, in-stock compounds ready for screening.
• The vIMS Library offers novel compounds with enhanced pharmacophoric diversity and improved drug-like characteristics.
• vIMS demonstrates unique chemical space compared to commercial virtual libraries.

Conclusions:

• Collaborative efforts between computational and synthetic chemists can yield cost-effective and resource-efficient chemical libraries.
• The developed chemoinformatics approach successfully generates tailored libraries (eIMS and vIMS) for pharmaceutical research.
• vIMS provides a valuable resource for expanding drug discovery efforts with novel, synthetically accessible compounds.