Label-free target identification reveals oxidative DNA damage as the mechanism of a selective cytotoxic agent.

ABSTRACT: Phenotypic screening can not only identify promising first-in-class drug candidates, but can also reveal potential therapeutic targets or neomorphic functions of known proteins. In this study, we identified target proteins of SB2001, a cytotoxic agent that acts specifically against HeLa human cervical cancer cells. Because SB2001 lacks chemical modification sites, label-free target identification methods including thermal stability shift-based fluorescence difference in two-dimensional gel electrophoresis (TS-FITGE) and thermal proteome profiling (TPP) were applied to characterize its mechanism of action. Owing to their differences, the two label-free target identification methods uncovered complementary target candidates. Candidates from both methods were prioritized according to their se

SUBMITTER: Park H 

PROVIDER: S-EPMC6438152 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature