The evolution of drug design at Merck Research Laboratories

Area of Science:

• Drug Discovery and Development
• Computational Chemistry
• Medicinal Chemistry

Background:

• Merck has over 40 years of experience in drug design, evolving from early computer-aided methods to a comprehensive
• The drug design group's evolution reflects a strategic shift towards integrating computational chemistry, protein structure determination, and cheminformatics.
• This integration aims to provide actionable hypotheses for experimental testing across various therapeutic modalities.

Purpose of the Study:

• To discuss the strategic evolution of Merck's drug design capabilities.
• To highlight the impact of aligning computational and experimental drug design efforts.
• To outline the development of a new strategy, skillsets, and metrics for continuous improvement in drug discovery.

Main Methods:

• Consolidation of computational chemistry, protein structure determination, and cheminformatics groups.
• Alignment of activities and capabilities across research sites and departments (2010-2016).
• Development of a "design first" approach across the drug discovery pathway, from lead identification to first in human dosing.

Main Results:

• An 80% expansion in the drug design department size, indicating increased impact.
• Enhanced ability to access data and create adaptive approaches for the lead identification to first in human pathway.
• Significant increase in the quality of drug candidates and their probability of success.

Conclusions:

• The "design first" strategy and integrated approach have been pivotal in advancing drug discovery at Merck.
• Continuous improvement is driven by strategic planning, appropriate skillsets, and defined success metrics.
• The alignment of diverse design disciplines enhances the efficiency and success rate of developing novel therapeutics.