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PTC-028

CAS No. : 1782970-28-8

產(chǎn)品活性：PTC-028 is an orally bioavailable inhibitor of stem cell factor BMI-1 in ovarian cancer. PTC-028 selectively inhibits cancer cells whereas normal cells remain unaffected. PTC-028 downregulates BMI-1, inducing caspase-mediated apoptosis.

研究領(lǐng)域：Apoptosis

作用靶點(diǎn)：Apoptosis

In Vitro: PTC-028 (25-500 nM; 48 hours) significantly decreases CP20, OVCAR4 and OV90 epithelial ovarian cancer cells viability. However, in normal ovarian surface epithelial cells (OSE) and fallopian tube epithelial cells (FTE) cells, up to 500 nM treatment with PTC-028 for 48 hours has minimal effect (~18-30% decrease).
PTC-028 (100 nM; 2-12 hours) increases the phosphorylated BMI-1 species in a time-dependent manner. PTC-028 subsequently reduces BMI-1 in the biochemical functional readout .
uH2A is observed up to 12 h with PTC-028 (100 nM) in both CP20 and OV90 cells while total H2A levels remain unchanged .
PTC-028 (100 nM; 48 hours) decreases the expression of XIAP and RIPK1 while LC3B levels remains unchanged compared to that of the control .
Significant cleavage of Caspase 7, Caspase 9 and PARP is observed in PTC-028 (100 nM; 48 hours).

In Vivo: PTC-028 (15 mg/kg; administered orally twice weekly) causes ~94% (0.169 g) reduction in tumor weight compared to the control (average tumor weight, ~3g) .
No obvious toxicity is noted in the animals during therapy experiments as assessed by mean body weight.
PTC-028 (10 mg/kg or 20mg/kg; single oral doses) is administrated to the CD-1 mice. The C_max is reached at both dose levels 1h post dose after which plasma concentrations slowly reduce.

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