The Screening Compound Collection: A Key Asset for Drug Discovery.

Area of Science:

• Drug Discovery
• Medicinal Chemistry
• Computational Chemistry

Background:

• Modern drug discovery relies on robust screening compound collections.
• Enhancing compound library quality is crucial for identifying viable drug candidates.

Purpose of the Study:

• To summarize efforts in enhancing the Actelion screening compound collection over four years.
• To detail the implementation and impact of a New Library Strategy.

Main Methods:

• Established a cross-functional Compound Library Committee (CLC) with a dedicated budget.
• Developed and implemented a New Library Strategy focusing on 'leadlike' structures, novelty, and diversity.
• Incorporated natural compounds, macrocycles, and focused libraries; engaged in compound exchanges.

Main Results:

• Increased structural library quality by shifting from 'druglike' to 'leadlike' criteria.
• Enriched the collection with non-flat structures, novel compounds, and premium compounds.
• Identified highly promising hits, including a macrocyclic compound, for further drug discovery programs.

Conclusions:

• The New Library Strategy successfully improved the screening compound collection's quality and diversity.
• The enhanced collection increases the likelihood of identifying successful early-stage drug discovery leads.
• The CLC's approach validates strategic library enhancement for drug discovery.