bmi1

Unesbulin (PTC596) is an orally active, selective inhibitor of B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1).

PTC-028 selectively suppresses cancer cells whereas normal cells remain unaffected. PTC-028 is an orally bioavailable inhibitor of stem cell factor BMI-1 in ovarian cancer. The depletion of BMI-1 by PTC-028 causes caspase-mediated apoptosis.

XMD8-92 is an effective and specific BMK1/ERK5 inhibitor (Kd: 80 nM).

PTC-209 is a potent and selective BMI-1 inhibitor.

PRT4165 (NSC600157) is a potent PRC1-mediated H2A ubiquitylation inhibitor.

PTC-209 hydrobromide (PTC-209 HBr) is the hydrobromide salt of PTC-209, which is a potent and selective BMI-1 inhibitor with IC50 of 0.5 μM, and results in irreversible reduction of cancer-initiating cells (CICs).

QW24 down-regulates BMI-1, exhibits potent antitumour effects and is used as an effective therapeutic agent in the treatment of clinical colorectal cancer.

SH498 is a novel Bmi-1-mediated anti-tumor agent with significant anti-proliferative effects.

1,6,7-Trihydroxyxanthone has anti-cancer activity ,at least in part, through the activation of miR-218 and suppression of Bmi-1 expression; can suppress cell growth and induce apoptosis in liver cancer cells.

PRC1-IN-1 (compound RB-4) is an inhibitor of the polycomb repressive complex 1 (PRC1) with an IC50 of 2.3 μM. It targets RING1B-BMI1, RING1A-BMI1, and RING1B-PCGF1, exhibiting IC50 values of 2.8 μM, 2.6 μM, and 1.8 μM, respectively.

MS147 is a VHL-based PROTAC PRC1 degrader. It shows binding affinity (Kd) of 3.0 μM to EED and 450 nM to VHL. The compound selectively targets the EED protein, a crucial component of PRC2, through its EED ligand portion, and interacts with PRC1 core components BMI1 and RING1B. This interaction enables MS147 to recruit BMI1 and RING1B near VHL, leading to their degradation. As a result, MS147 reduces the ubiquitination level of H2AK119ub, thereby impacting the proliferation of cancer cells.

MS181 (compound 1) is an efficient PROTAC degrader that recruits cereblon (CRBN) and binds to the ubiquitin complex polycomb repressive complex 1 (PRC1). It reduces the expression of EED, EZH2, SUZ12, BMI1, and RING1B, and exhibits antiproliferative activity.