A Gold-PROTAC Degrades the Oncogenic Tyrosine Kinase MERTK: Insights into the Degradome from a Steady-State System.

ABSTRACT: Proteolysis targeting chimeras (PROTACs) are bifunctional molecules designed to induce the degradation of specific proteins within a cell. While most PROTACs are noncovalent interactors, covalent PROTACs may benefit from improved selectivity and pharmacodynamics, yet remain largely understudied. Here, a covalent gold-based PROTAC (AuPROTAC) was synthesized, featuring a Au(III)-warhead, known to induce cysteine-arylation in a gold-templated two-step mechanism, linked to a cereblon binding moiety. The degradome of the AuPROTAC was characterized by establishing a cycloheximide chase assay in a nonproliferative steady-state HL-60 cell culture, enabling the identification of PROTAC degradation targets uncoupled from confounding effects originating from cell-cycle-dependent transla

SUBMITTER: Thomas SR 

PROVIDER: S-EPMC12813982 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature