Fragonomics: fragment-based drug discovery.

Area of Science:

• Drug discovery and development
• Medicinal chemistry
• Biochemistry

Background:

• Fragment-based drug discovery (FBDD) has emerged as a successful strategy for identifying novel drug leads.
• This approach involves using smaller molecules, known as fragments, to target various biological entities.
• FBDD integrates library design, screening, and medicinal chemistry for lead optimization.

Purpose of the Study:

• To provide an overview of the fragment-based drug discovery process.
• To highlight the critical role of screening in identifying initial fragment hits.
• To emphasize the application and importance of nuclear magnetic resonance (NMR) in fragment screening.

Main Methods:

• Overview of library design principles for fragment-based screening.
• Description of various screening methodologies employed in FBDD.
• Detailed explanation of nuclear magnetic resonance (NMR) spectroscopy techniques for fragment screening and analysis.

Main Results:

• Fragment-based approaches have proven effective in generating starting points for drug development against diverse targets.
• NMR screening provides valuable biophysical data for hit identification and validation.
• The integration of NMR with other techniques enhances the efficiency of the FBDD pipeline.

Conclusions:

• Fragment-based drug discovery is a powerful strategy for identifying novel therapeutic leads.
• NMR is an indispensable tool in fragment screening, enabling detailed molecular insights.
• The described integrated process facilitates the progression of fragments into optimized drug candidates.