Background

OTUD7B is a deubiquitinase that regulates inflammation, T-cell activation, and cell signaling pathways that promote tumor progression in various cancers. However, its function in cancer remains largely unknown, and a few deubiquitinase inhibitors have been developed due to technical challenges.

Technology Overview

UNC researchers discovered a series of compounds that selectively inhibit the catalytic activity of OTUD7B deubiquitinase using an AI-aided screen of a 4 million compound library. The lead compound, 7Bi, demonstrated anti-oncogenic activity and inhibited cell growth in multiple non-small cell lung cancer & leukemia cell lines via selectively blocking OTUD7B-induced deubiquitination. In the non-small cell lung cancer (NSCLC) model, the 7Bi treatment increased ubiquitination K63-linked ubiquitination of GβL, which attenuated mTORC2 kinase complex formation, thus weakening