Ubiquitin-specific protease 9, X-linked (USP9X) is a highly conserved cysteine protease that regulates multiple key developmental cellular signalling pathways. Elevated USP9X activity correlates with tumour progression and poor prognosis in multiple cancers, including pancreatic ductal adenocarcinoma (PDA) and brain cancer; two malignancies with the lowest five-year survival rate. Genetic ablation of USP9X promotes cancer cell apoptosis and sensitizes cancer cells to chemo- and radiotherapy. As such, USP9X has been proposed as a promising therapeutic target. We recently solved the crystal structure of the catalytic domain of USP9X and identified a druggable pocket.
We aim to combine artificial intelligence and protein biochemistry to discover novel drug candidates targeting USP9X for cancer treatment.