Poster: Enabling VPS4B Drug Discovery Through a Robust and Miniaturized ATPase Screening Platform

Vacuolar protein sorting–associated protein 4B (VPS4B) is a meiotic clade AAA ATPase implicated in cancer biology through its overexpression in select tumors and a synthetic-lethal relationship with its paralog, VPS4A. These features make VPS4B an attractive therapeutic target, yet robust and scalable screening approaches for VPS4B inhibitors remain limited. Here, we describe the development of a miniaturized, high-throughput screening (HTS) platform for discovery and profiling of VPS4B ATPase inhibitors. ATPase activity was quantified using the Transcreener® ADP² fluorescence polarization assay, which enables direct, homogeneous detection of ADP with high sensitivity and minimal assay interference.