Drug affinity responsive target stability (DARTS) accelerated small molecules target discovery: Principles and...

Area of Science:

• Biochemistry
• Pharmacology
• Drug Discovery

Background:

• Drug affinity responsive target stability (DARTS) is a novel approach for identifying targets of small molecules (SMs).
• It functions by monitoring protein stability changes upon bioactive SM binding, without needing structural modifications.
• DARTS is effective in screening targets directly from cellular or tissue samples.

Purpose of the Study:

• To review the analytical principles, protocols, validation methods, applications, and challenges of the DARTS technique.
• To highlight the utility of DARTS in understanding drug-action mechanisms.
• To emphasize its potential in accelerating small molecule target discovery.

Main Methods:

• The review summarizes the core principles of DARTS, focusing on how protein stability changes indicate drug-target interactions.
• It details established protocols for implementing the DARTS assay.
• Validation approaches and diverse applications of DARTS are discussed.

Main Results:

• DARTS enables the identification of drug-target interactions by assessing protein stability shifts.
• The method has been successfully applied to elucidate drug-action mechanisms.
• Its efficiency and ease of use make it suitable for complex biological matrices.

Conclusions:

• DARTS is a potent tool for small molecule target discovery, particularly for bioactive natural products with unknown mechanisms.
• The technique offers significant advantages for accelerating the identification of drug targets.
• Further application and refinement of DARTS are expected to advance drug discovery pipelines.