[From high content screening to target deconvolution: New insights for phenotypic approaches]

Area of Science:

• Pharmaceutical Science
• Molecular Biology
• Drug Discovery

Background:

• The pharmaceutical industry initially adopted target-centric drug discovery following advances in molecular biology and genomics.
• Declining R&D productivity and technological progress have spurred a resurgence in phenotypic drug discovery.
• High-content screening, automation, image analysis, and AI are key drivers of this shift.

Purpose of the Study:

• To review the evolution of target-centric and phenotypic drug discovery approaches.
• To highlight the role of high-content screening and target deconvolution technologies.
• To emphasize the complementary nature of these two discovery strategies.

Main Methods:

• Literature review of target-centric and phenotypic drug discovery.
• Analysis of technological advancements in screening and analysis.
• Focus on target deconvolution methodologies.

Main Results:

• Phenotypic drug discovery is regaining prominence due to technological advancements.
• Target-centric and phenotypic approaches are increasingly viewed as complementary.
• Target deconvolution is a critical enabling technology for integrated drug discovery.

Conclusions:

• The integration of target-centric and phenotypic drug discovery offers a more robust pipeline.
• Advancements in high-content screening and AI are enhancing phenotypic approaches.
• Effective target deconvolution is essential for maximizing the benefits of both strategies.