3-deazaneplanocin A HCl 是组蛋白甲基转移酶 (EZH2) 和 S-腺苷同型半胱氨酸水解酶 (AHCY) 抑制剂。

3-deazaneplanocin A HCl is both an S-adenosyl-l-homocysteine hydrolase inhibitor and an enhancer of zeste homolog 2(EZH2) inhibitor.

EZH2 expression was detected by quantitative PCR in 15 PDAC cells, including seven primary cell cultures, showing that expression values correlated with their originator tumors (Spearman R(2) = 0.89, P = 0.01). EZH2 expression in cancer cells was significantly higher than in normal ductal pancreatic cells and fibroblasts. The 3-deazaneplanocin A HCl(5 μmol/L, 72-hour exposure) modulated EZH2 and H3K27me3 protein expression and synergistically enhanced the antiproliferative activity of gemcitabine, with combination index values of 0.2 (PANC-1), 0.3 (MIA-PaCa-2), and 0.7 (LPC006). The drug combination reduced the percentages of cells in G(2)-M phase (e.g., from 27% to 19% in PANC-1, P< 0.05) and significantly increased apoptosis compared with gemcitabine alone. Moreover, 3-deazaneplanocin A HCl enhanced the mRNA and protein expression of the nucleoside transporters hENT1/hCNT1. 3-deazaneplanocin A HCl decreased cell migration, which was additionally reduced by 3-deazaneplanocin A HCl/gemcitabine combination (-20% in LPC006, after 8-hour exposure, P< 0.05) and associated with increased E-cadherin mRNA and protein expression. Furthermore, 3-deazaneplanocin A HCl and 3-deazaneplanocin A HCl/gemcitabine combination significantly reduced the volume of PDAC spheroids growing in CSC-selective medium and decreased the proportion of CD133+ cells[2].

The survival of NOD/SCID mice with AML due to HL-60 cells was significantly higher, if treated with 3-deazaneplanocin A HCl and PS compared to treatment with PS, 3-deazaneplanocin A HCl, or vehicle alone (P< .05). Cotreatment with 3-deazaneplanocin A HCl and PS also did not increase the weight loss in the mice. Median survival was as follows: control, 36 days; PS, 42 days; 3-deazaneplanocin A HCl, 43 days; and 3-deazaneplanocin A HCl plus PS, 52 days.Compared with treatment with each agent alone, combined treatment with 3-deazaneplanocin A HCl and PS improved survival of NOD/SCID mice with leukemia caused by the AML HL-60 cells[3].

120964-45-6

C12H15ClN4O3

298.73

H2O:50 mg/mL (167.38 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years