Monitoring drug-target interactions through target engagement-mediated amplification on arrays and in situ.

ABSTRACT: Drugs are designed to bind their target proteins in physiologically relevant tissues and organs to modulate biological functions and elicit desirable clinical outcomes. Information about target engagement at cellular and subcellular resolution is therefore critical for guiding compound optimization in drug discovery, and for probing resistance mechanisms to targeted therapies in clinical samples. We describe a target engagement-mediated amplification (TEMA) technology, where oligonucleotide-conjugated drugs are used to visualize and measure target engagement in situ, amplified via rolling-circle replication of circularized oligonucleotide probes. We illustrate the TEMA technique using dasatinib and gefitinib, two kinase inhibitors with distinct selectivity profiles. In vitro binding by the

SUBMITTER: Al-Amin RA 

PROVIDER: S-EPMC9825164 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature