| 应用 |
IC50: Inhibit tumor cells growth with an IC50of about 4 M.
Being defective for the tumor-suppressor function, mutant p53, a major contributor to malignancy, exerts oncogenic activity also by blocking another tumor-suppressing protein - p73. RETRA hydrochloride is considered to restore mutant p53 activity and therefore to inhibit growth of carcinoma cells. This small molecular could also transcriptionally up-regulates the expression of p53-responsive gene and induces the activation of caspases 3 and 7. RETRA’s anticancer activity is restricted to tumor cells bearing mutant p53.
In vitro: Ewing’s sarcoma (ES) cells with mutant p53 were explored to RETRA, it was found that this compound could substantially up-regulate the expression level of p73 and therefore increase the apoptosis of tumor cells in three mutant p53 ES cell lines. In addition, RETRA was described to activate a set of p53-regulated genes in vitro. However, for most of the p53-deficient carcinoma, osteosarcoma and leukaemia cells, RETRA had no significant effect.
In vivo: Effect of RETRA hydrochloride was studied in vivo using mouse xenografts model. It was noticed that mutant p53-bearing tumor cells were specifically suppressed with a significantly increase in the p73 level and a release of p73 from the blocking complex with mutant p53.
Clinical trial: So far, no clinical study has been conducted. |
