Target-based drug discovery: Applications of fluorescence techniques in high throughput and fragment-based screening

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Understanding disease mechanisms requires precise measurement of biomolecular activities.
• Altered biomolecule function in disease necessitates robust assay techniques.
• Developing therapeutic interventions relies on modulating molecular processes.

Purpose of the Study:

• To review fluorescence-based techniques for drug discovery.
• To highlight applications in high throughput screening (HTS) and fragment-based ligand discovery (FBLD).
• To discuss advancements in screening compound libraries against key drug targets.

Main Methods:

• Fluorescence polarization (FP)
• Förster resonance energy transfer (FRET)
• Fluorescence thermal shift assay (FTSA)
• Microscale thermophoresis (MST)

Main Results:

• These techniques facilitate the discovery of chemical probes for disease biology.
• Advancements enable screening against G-protein-coupled receptors (GPCRs), GTPases, and protein-protein interactions.
• Successful application in identifying small-molecule modulators and biologics.

Conclusions:

• Fluorescence-based HTS and FBLD are foundational for drug discovery.
• These methods accelerate the identification of therapeutic agents.
• They provide a pathway for developing novel treatments for various diseases.