unesbulin

Unesbulin (PTC596) is an orally bioavailable small molecule inhibitor designed to target cancer stem cells by reducing the levels of BMI1 (B-cell-specific Moloney murine leukemia virus integration site 1). BMI1 is a core component of the Polycomb Repressive Complex 1 (PRC1), which is essential for the self-renewal and survival of cancer stem cells and is often associated with poor prognosis and resistance to conventional therapies. Unesbulin's mechanism of action involves the inhibition of microtubule polymerization, which induces cell cycle arrest at the G2/M phase and leads to the subsequent degradation of BMI1 protein. Developed by PTC Therapeutics, the drug has been investigated in clinical trials for various cancers, including leiomyosarcoma, diffuse intrinsic pontine glioma (DIPG), and acute myeloid leukemia (AML). In 2022, PTC Therapeutics announced the discontinuation of the Phase 2/3 FIESTA-LMS trial in leiomyosarcoma after the study failed to meet its primary endpoint of progression-free survival.

Other names

unesbulin