PTC-596

Research use only, not for human use.

PTC-596 (PTC596)?is a novel, orally active, small molecule inhibitor of BMI-1 that accelerates BMI-1 degradation, inhibits AML cells growth with IC50 of <100 nM.

PTC-596 (PTC596)?is a novel, orally active, small molecule inhibitor of BMI-1 that accelerates BMI-1 degradation, inhibits AML cells growth with IC50 of <100 nM; PTC-596 is a direct microtubule polymerization inhibitor; reduces total BMI-1 protein levels by 87% and 61% in MOLM-13 and OCI-AML3 cells at 100 nM, induces apoptosis and reduces the levels of ubiquitylated histone H2A; downregulates MCL-1 and induces p53-independent mitochondrial apoptosis in acute myeloid leukemia progenitor cells.Ovarian Cancer Phase 1 Clinical.

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. Unesbulin (200?nM; for 10?hours) leads to an accumulation of cells in G2/M phase. Unesbulin (0.012-1 μM; for 20?hours) significantly reduces protein levels of BMI-1. Unesbulin inhibits APC/CCDC20 activity resulting in the persistent activation of CDK1 and CDK2 which mediate the hyperphosphorylation of BMI1. Apoptosis Analysis Cell Line:AML cell lines (MOLM-13, OCI-AML3, MOLM-14, MV4-11, U-937, HL-60) .Concentration:20, 50, 100, 200?nM .Incubation Time:For 48?hours Result:Induced apoptosis in a dose- and time-dependent manner with the average IC50 and ED50 values among six cell lines were 30.7?nM and 60.3?nM, respectively.Cell Cycle Analysis Cell Line:MOLM-13 and U-937 cells Concentration:200?nM.Incubation Time:For 10?hours Result:Led to an accumulation of cells in G2/M phase, whereas the percentage of cells in G1 phase decreased.Western Blot Analysis Cell Line:MOLM-13 cell. Concentration:0.012, 0.037, 0.11, 0.33, 1 μM .Incubation Time:For 20?hours Result:Significantly reduced protein levels of BMI-1 and its downstream target ubiquitinated histone H2A. .Increased cyclin B1 and securin levels.

Unesbulin (PTC596; 5?mg/kg; oral gavage; every 3 days for 13 days) significantly prolongs mouse survival. 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. 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. Animal Model:NOD-SCID/IL2Rγ-KO (NSG) mice with MOLM-13 cellsDosage:5?mg/kg Administration:Oral gavage; every 3 days for 13 days Result:Significantly prolonged mouse survival compared with the vehicle-treated mice in a dose-dependent manner.

PTC 596 | PTC596

Others

BMI-1

BMI-1

Cancer

Ovarian Cancer

1610964-64-1

420.347

C19H13F5N6

>98% (HPLC)

In Vitro:?DMSO : 16.67 mg/mL (39.66 mM)

NC1=C(F)C(NC2=CC=C(C(F)(F)F)C=C2)=NC(N3C4=CC(F)=CC=C4N=C3C)=N1

5-fluoro-2-(6-fluoro-2-methyl-1H-benzo[d]imidazol-1-yl)-N4-(4-(trifluoromethyl)phenyl)pyrimidine-4,6-diamine

(-20℃)

With Ice Pack

≥ 2 years