Targeting DYRK2 for prostate cancer

An inhibitor of the cytoplasmic kinase DYRK2, which has dual tyrosine and serine/threonine kinase activity, could help treat prostate cancer. Bioinformatic analysis of data from The Cancer Genome Atlas showed DYRK2 was more highly expressed in samples from prostate cancer patients than from healthy controls, and in patient samples, DYRK2 expression was higher in tumor cells than non-tumor cells, and low expression of DYRK2 was associated with greater survival.

A structure-based virtual screen of 195,483 compounds identified 15 candidate DYRK2 inhibitors, among which the top hit inhibited DYRK2 with an IC50 of 263 nM. Subsequent optimization yielded a compound with a benzothiazole chemical scaffold that inhibited DYRK2 with an IC50 of 9 nM, and had 100-fold selectivity for DYRK2 over other DYRK proteins...