PTC-028 是一种口服有效的干细胞因子BMI-1的抑制剂，可下调 BMI-1，诱导 Caspase 介导的细胞凋亡。它选择性地抑制癌细胞，可用于治疗卵巢癌。

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.

PTC-028 subsequently decreases BMI-1 in the biochemical functional readout. PTC-028 (100 nM; 2-12 hours) increases the phosphorylated BMI-1 species in a time-dependent manner. 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 remain unchanged compared to that of the control. PTC-028 (25-500 nM; 48 hours) obviously reduces CP20, OVCAR4, and OV90 epithelial ovarian cancer cell 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 a minimal effect (~18-30% decrease). Significant cleavage of Caspase 7, Caspase 9, and PARP is observed in PTC-028 (100 nM; 48 hours)[1].

PTC-028 (10 mg/kg or 20mg/kg; single oral doses) is administrated to the CD-1 mice. The Cmax is reached at both dose levels 1h post-dose after which plasma concentrations slowly decrease. PTC-028 (15 mg/kg; administered orally twice weekly) induces ~94% (0.169 g) reduction in tumor weight compared to the control (average tumor weight, ~3g) [1].

1782970-28-8

C19H12F5N5

405.32

DMSO:125 mg/mL (308.40 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years