STPP-UP: An alternative method for drug target identification using protein thermal stability

Area of Science:

• Biochemistry
• Pharmacology
• Proteomics

Background:

• Thermal proteome profiling (TPP) aids drug discovery by identifying protein targets.
• Current TPP methods are labor-intensive and time-consuming, limiting high-throughput screening.
• A need exists for more efficient TPP techniques.

Purpose of the Study:

• To introduce Single-tube TPP with Uniform Progression (STPP-UP) as an improved TPP method.
• To reduce sample input and measurement time for TPP.
• To maintain TPP's capability in identifying drug targets.

Main Methods:

• STPP-UP utilizes incremental heating of a single sample.
• This allows assessment of protein thermal stability changes across temperatures.
• Eliminates the need for multiple samples heated separately.

Main Results:

• STPP-UP significantly decreases required input material and measurement time.
• The method successfully identifies direct interactors for anticancer drugs.
• Demonstrated efficacy in both human and mouse cells.

Conclusions:

• STPP-UP is a valuable tool for drug discovery and repurposing.
• The methodology enhances the efficiency of target identification.
• Advances the application of TPP in high-throughput screening.