Alternative variables in drug discovery: promises and challenges

Area of Science:

• Medicinal Chemistry
• Drug Discovery
• Pharmacokinetics

Background:

• Lipinski's guidelines aim to predict drug-likeness but have limitations.
• Existing ligand efficiency metrics vary in formulation and success.
• Need for a unified approach to assess pharmacokinetic properties early in drug discovery.

Purpose of the Study:

• To introduce and validate a unified formulation for ligand efficiency indices.
• To demonstrate the utility of these indices in optimizing the drug discovery process.
• To present a novel methodology for multiparameter optimization in drug development.

Main Methods:

• Development of ligand efficiency indices incorporating size and polarity.
• Application of these indices within an extended multiparameter optimization framework.
• Utilizing the AtlasCBS platform for mapping and monitoring drug discovery.

Main Results:

• The proposed ligand efficiency indices provide a more rigorous assessment of drug-likeness.
• Integration with multiparameter optimization enhances the efficiency of the drug discovery pipeline.
• Demonstrated success in optimizing drug discovery processes through case examples.

Conclusions:

• Ligand efficiency indices offer a promising, unified approach to medicinal chemistry challenges.
• This methodology facilitates early identification and exclusion of compounds with poor pharmacokinetic properties.
• Future drug discovery efforts can benefit from this advanced optimization strategy.