Exploring new targets and chemical space with affinity selection-mass spectrometry

Area of Science:

• Drug Discovery and Development
• Biochemistry and Molecular Biology
• Analytical Chemistry

Background:

• High-throughput screening (HTS) is crucial for identifying drug leads.
• Traditional HTS methods may face limitations with certain biological targets.
• Novel screening approaches are needed to explore diverse chemical spaces.

Purpose of the Study:

• To highlight the utility of Affinity Selection-Mass Spectrometry (AS-MS) in drug discovery.
• To showcase AS-MS as a method for identifying ligands against challenging targets.
• To illustrate the potential of AS-MS in delivering high-quality hits for optimization.

Main Methods:

• AS-MS is a binding assay enabling rapid screening of compound libraries.
• The technique is insensitive to ligand functional effects, allowing identification of novel binding sites.
• AS-MS facilitates exploration of broad chemical space for ligand discovery.

Main Results:

• AS-MS has emerged as a key HTS approach in drug discovery.
• The method has been instrumental in developing agents for targeted protein degradation.
• Reported AS-MS hits demonstrate the potential for high-quality lead identification.

Conclusions:

• AS-MS is a versatile and increasingly popular HTS technique.
• It offers a valuable alternative to traditional screening paradigms, especially for difficult targets.
• AS-MS is establishing itself as a mainstream HTS approach for drug discovery.