Unesbulin

Unesbulin (PTC596) is an orally active and selective B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) inhibitor. Unesbulin downregulates MCL-1 and induces p53-independent mitochondrial apoptosis in acute myeloid leukemia (AML) cells. Unesbulin has anti-leukemic activity^[1][2]. IC50 & Target: BMI-1^[1] In Vitro: Unesbulin (PTC596; 20-200?nM; for 48?hours) induces apoptosis in AML cells in a p53-independent manner. BMI-1 overexpression desensitizes AML cells to PTC596-induced apoptosis^[1].
Unesbulin (200?nM; for 10?hours) leads to an accumulation of cells in G2/M phase^[1].
Unesbulin (0.012-1 μM; for 20?hours) significantly reduces protein levels of BMI-1^[1].
Unesbulin inhibits APC/CCDC20 activity resulting in the persistent activation of CDK1 and CDK2 which mediate the hyperphosphorylation of BMI1^[2].
In Vivo: Unesbulin (PTC596; 5?mg/kg; oral gavage; every 3 days for 13 days) significantly prolongs mouse survival^[1].
Unesbulin (20?mg/kg; oral gavage; once a week for 15 days) causes tumor volume significantly smaller than that of control SCID mice with K562 cells^[1].
Unesbulin (10 or 12.5 ?mg/kg; oral gavage; twice a week until death) causes the survival significantly longer than the vehicle-treated group in NOD-SCID mice with HL-60 cells^[1].