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Target-based drug discovery: is something wrong?

Frank Sams-Dodd¹

¹Boehringer Ingelheim Pharma, GmbH & Co KG, D-88397, Biberach, Germany. frank.sams-dodd@bc.boehringer-ingelheim.com

Drug Discovery Today

|February 19, 2005

Summary

Target-based drug discovery, despite its screening advantages, may not have boosted pharmaceutical productivity due to complex target validation. This analysis explores potential weaknesses in target validation compared to traditional in vivo methods.

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Area of Science:

Pharmaceutical industry
Drug discovery
Medicinal chemistry

Background:

Pharmaceutical productivity has declined over the past decade.
This decline coincided with the introduction of target-based drug discovery.
Target-based approaches excel at developing treatments for validated targets.

Purpose of the Study:

To analyze the complexities and uncertainties in target validation.
To determine if target validation weaknesses explain the lack of productivity increase.
To compare target-based drug discovery with traditional in vivo approaches.

Main Methods:

Analysis of target validation processes.
Comparison of screening capacity between target-based and in vivo approaches.

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Evaluation of rational drug discovery program definition.

Main Results:

Target validation is a complex process with inherent uncertainty.
The introduction of target-based drug discovery has not demonstrably increased overall productivity.
Traditional in vivo approaches possess advantages in screening capacity and program definition.

Conclusions:

Weaknesses in target validation may hinder the success of target-based drug discovery.
The paradigm shift to target-based discovery requires re-evaluation of its productivity impact.
Further research is needed to optimize target validation and drug discovery strategies.