Cymipristone

To investigate the antiproliferative activity of a new synthetic steroid ZXH951 structurally related to mifepristone (RU486) and its effects on cell cycle traverse and telomerase activity in human breast carcinoma cell lines.

Antiproliferative activity was determined by cell growth curve, MTT reduction and colony formation. Receptor binding affinities were measured by competitive binding assay using radiolabelled ligands. Cell cycle distribution was analyzed by flow cytometry. Telomerase activity was investigated by TRAP-PCR.

ZXH951 exhibited potent antiproliferative activity in estrogen receptor and progesterone receptor positive human breast carcinoma cell lines in vitro, high affinity with human progesterone receptor-A, little affinity with estrogen receptor and blockade the cells in G1 phase. Moreover, when T47D cells were exposed to 0.4, 1.0 and 10 mumol.L-1 of ZXH951 for 72 h, the telomerase activity was significantly decreased.

ZXH951 is a promising progesterone receptor antagonist. It significantly inhibits the growth of estrogen receptor and progesterone receptor positive human breast carcinoma cells. Its mechanism of action may be related to its antiproliferation mediated by progesterone receptor and inhibition of telomerase activity.

Objective: To observe the effect of samistone on terminating early pregnancy of rhesus monkeys and its impact on the amount of vaginal bleeding, provide an exptl. basis for researching and developing new drugs.Methods: The pregnant rhesus monkeys were randomly divided into seven groups: the rhesus monkeys in samistone group and mifepristone group were divided into low-dose group, middle-dose group, and high-dose group (5 mg·kg-1·d-1, 10 mg·kg-1·d-1, and 15 mg·kg-1·d-1), resp.; excipient (0.5% sodium CM-cellulose) group was designed, five rhesus monkeys in each group.The rhesus monkeys in samistone group and mifepristone group were treated with different doses of samistone and mifepristone in a fasting state on the 42nd-48th day during menstrual cycle, once a day for three days, 200 μg misoprostol was administrated on the fourth day; the adverse reactions were observed after treatment, B ultrasound was applied to predict abortion and development of embryos on the fifteenth day.Results: The complete abortion rates in high-dose samistone group and middle-dose samistone group were 60.00% (3/5) and 20.00% (1/5), resp.; while in low-dose samistone group, no abortion occurred.The complete abortion rates in high-dose mifepristone group, middle-dose mifepristone group, and low-dose mifepristone group were 80.00% (4/5), 40.00% (2/5), and 20.00% (1/5), resp.The total abortion rates in samistone group and mifepristone group were 26.67% (4/15) and 46.67% (7/15), there was no statistically significant difference between the two groups (P > 0.05).The duration time of vaginal bleeding in samistone group was significantly shorter than that in mifepristone group, the amount of vaginal bleeding in samistone group was significantly less than that in mifepristone group (P < 0.05).Conclusion: Samistone can terminate early pregnancy of rhesus monkeys, shorten the bleeding time, and reduce the amount of vaginal bleeding obviously.