Large-scale characterization of drug mechanism of action using proteome-wide thermal shift assays.

ABSTRACT: In response to an ever-increasing demand of new small molecules therapeutics, numerous chemical and genetic tools have been developed to interrogate compound mechanism of action. Owing to its ability to approximate compound-dependent changes in thermal stability, the proteome-wide thermal shift assay has emerged as a powerful tool in this arsenal. The most recent iterations have drastically improved the overall efficiency of these assays, providing an opportunity to screen compounds at a previously unprecedented rate. Taking advantage of this advance, we quantified more than one million thermal stability measurements in response to multiple classes of therapeutic and tool compounds (96 compounds in living cells and 70 compounds in lysates). When interrogating the dataset as a whole, approx

SUBMITTER: Van Vranken JG 

PROVIDER: S-EPMC10849652 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature