From fragment to clinical candidate--a historical perspective

Area of Science:

• Drug Discovery and Development
• Medicinal Chemistry
• Biotechnology

Background:

• Fragment-based drug discovery (FBDD) has evolved significantly over the past decade.
• Low molecular weight fragments (<300 MW) with weak binding affinities are now recognized as viable starting points for drug development.
• FBDD is now an established strategy in the pharmaceutical and biotechnology industries.

Purpose of the Study:

• To provide a historical overview of the development of fragment-based drug discovery.
• To highlight the increasing acceptance and integration of FBDD as a complementary strategy to high-throughput screening.
• To showcase clinical compounds that have resulted from FBDD approaches.

Main Methods:

• Historical review of fragment-based drug discovery evolution.
• Analysis of the progression of fragment hits into lead series and clinical candidates.
• Case studies of clinical compounds discovered through FBDD.

Main Results:

• Fragment-based drug discovery has rapidly gained acceptance in the scientific community.
• Weakly binding, low molecular weight fragments are now considered valuable starting points.
• Several clinical compounds have been successfully developed using FBDD.

Conclusions:

• Fragment-based drug discovery is a validated and effective strategy in modern drug discovery.
• FBDD offers a complementary approach to traditional high-throughput screening.
• The success of FBDD is evidenced by its contribution to clinical drug candidates.