Utilizing the HiBiT System to Identify CARM1 Degraders for Targeted Cancer Therapy.

ABSTRACT: Preclinical studies validated coactivator-associated arginine methyltransferase 1 (CARM1) as a targetable therapeutic vulnerability, leading to the development of Proteolysis-Targeting Chimeras that specifically degrade CARM1. These compounds face significant translational challenges, including poor oral bioavailability and limited metabolic stability, which require extensive optimization. To identify more drug-like CARM1 degraders, we developed a high-throughput screening platform. We enabled antibody-free monitoring of CARM1 levels by fusing a HiBiT tag to CARM1 in MCF7 breast cancer cells. Complementation with LgBiT produces luciferase activity. Using this platform, we screened 1408 plant-derived natural product fractions to identify compounds that reduce CARM1 protein levels. This scre

SUBMITTER: Bacabac M 

PROVIDER: S-EPMC12794155 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature