Introduction to biological complexity as a missing link in drug discovery

Area of Science:

• Drug discovery and development
• Pharmacology
• Medicinal chemistry

Background:

• Despite advances in understanding disease mechanisms and drug screening technologies, identifying novel pharmacologic therapies remains difficult.
• A key challenge is the inability to scale and integrate biological responses from simple model systems to complex, human-based systems.

Purpose of the Study:

• To identify the disconnect hindering novel drug discovery.
• To propose strategies for advancing drug development by integrating data across biological scales.

Main Methods:

• Review of primary literature and concepts from academic and industrial drug screening.
• Analysis of the challenges in scaling and integrating biological data across different system complexities.

Main Results:

• The disconnect in drug discovery stems from the inability to effectively integrate data across scales, from simple models to human systems.
• Attempts to integrate mechanistic and observational data across scales highlight gaps in understanding as complexity increases.

Conclusions:

• Future drug discovery necessitates collaborative efforts combining target-based, phenotypic-based, and systems-based pharmacology with informatics.
• Rethinking the application of enabling technologies and asking new questions are crucial for advancing drug development and deriving novel drug candidates.