BMI-1

BMI-1 inhibitors target a Polycomb group protein that silences genes and supports stem cell self-renewal. B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is a core subunit of Polycomb repressive complex 1 (PRC1). In 2004, PRC1 was shown to monoubiquitinate histone H2A, a mark linked to Polycomb silencing. A 2003 mouse study found BMI-1 to be required for maintaining adult self-renewing hematopoietic stem cells. PTC-209 lowers BMI-1 protein levels and was used in 2014 to study self-renewal of colorectal cancer-initiating cells. PTC-028 and unesbulin are two further compounds listed here as BMI-1 inhibitors. PRT 4165 instead inhibits the ubiquitin ligase activity of the complex of BMI-1 with its partner ring finger protein 1A (RING1A).