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

Thermal proteome profiling (TPP) has significantly advanced the field of drug discovery by facilitating proteome-wide identification of drug targets and off-targets. However, TPP has not been widely applied for high-throughput drug screenings, since the method is labor intensive and requires a lot of measurement time on a mass spectrometer. Here, we present Single-tube TPP with Uniform Progression (STPP-UP), which significantly reduces both the amount of required input material and measurement time, while retaining the ability to identify drug targets for compounds of interest.

热蛋白质组分析（Thermal proteome profiling, TPP）通过支持全蛋白质组范围内的药物靶点与脱靶靶点鉴定，极大推动了药物发现领域的发展。然而，由于该方法劳动强度大且需要在质谱仪上耗费大量检测时长，TPP尚未被广泛应用于高通量药物筛选。本研究提出了单管均匀进度热蛋白质组分析（Single-tube TPP with Uniform Progression, STPP-UP），该方法在保留目标化合物药物靶点鉴定能力的同时，大幅降低了所需的起始材料投入量与检测时长。