A novel ROR1-targeting antibody-PROTAC conjugate promotes BRD4 degradation for solid tumor treatment.

ABSTRACT: Rationale: Proteolysis Targeting Chimeras (PROTACs) are bifunctional compounds that have been extensively studied for their role in targeted protein degradation (TPD). The capacity to degrade validated or undruggable targets provides PROTACs with significant potency in cancer therapy. However, the clinical application of PROTACs is limited by their poor in vivo potency and unfavorable pharmacokinetic properties. Methods: In this study, a novel degrader-antibody conjugate (DAC) was developed by conjugating the BRD4-degrading PROTAC with the ROR1 (receptor tyrosine kinase-like orphan receptor 1) antibody. The in vitro affinity, internalization efficacy, degradation, and cytotoxic activity of the ROR1 DAC were assessed. The pharmacokinetics, antitumor activity, and

SUBMITTER: Wang L 

PROVIDER: S-EPMC11729552 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature