Discovery of a First-in-Class MPP8 Antagonist to Reverse Lineage Plasticity in Bladder Cancer
Abstract
Bladder cancer (BC) is a common and deadly disease, and despite recent treatment advances, metastatic BC (mBC) remains incurable. Mutations in genes that encode epigenetic/chromatin modifier proteins are common in mBC, with >90% of tumors harboring at least one inactivating mutation. The epigenetic reader protein MPP8 recognizes the histone-3-lysine-9-trimethyl(H3K9me3) region of target gene promoters, and recruits transcription factors associated with cell proliferation and metastasis. UNC7713 was developed as a covalent antagonist to disrupt MPP8 binding to H3K9me3. Here, we explored whether UNC7713 potently inhibits cell proliferation, migration, and viability in preclinical models of BC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1199708
Entities
People
- Daniel J. Crona
Organizations
- University of North Carolina at Chapel Hill