Mifepristone

Mifepristone (RU486) is a potent antagonist of progesterone receptor, used as a contraceptive agent [1].

As a contraceptive agent, Mifepristone has been reported to reduce the size of uterine fibroids, and inhibit the growth of meningioma cells in vitro, in experimental animal models and in patients with inoperable meningiomas. As a non-contraceptive action, Mifepristone was been revealed to inhibit the proliferation of normal and malignant endometrial cells, breast cancer cells, prostate cancer cells and gastric adenocarcinoma cell lines. In addition, Mifepristone has been demonstrated to have progesterone-like effects and suppression ovarian cancer cell growth in a dose-dependent fashion with the IC50 values of 6.25μmol/l and 6.91μmol/l for SK-OV-3 and OV2008 cell lines, respectively [1].

References:
[1] Goyeneche AA1, Carón RW, Telleria CM. Mifepristone inhibits ovarian cancer cell growth in vitro and in vivo. Clin Cancer Res. 2007 Jun 1; 13(11):3370-9.

Effect of Mifepristone on Corticosteroid Production in Vitro by Adrenal Glands of Rats with Streptozotocin Diabetes.[Pubmed:28091906]

Bull Exp Biol Med. 2017 Jan;162(3):327-330.

Changes in pregnenolone and corticosterone production by the adrenal glands of normoglycemic rats receiving the course of intraperitoneal Mifepristone or NaCl administration were co-directed, but differed in magnitude. In rats with hyperglycemia, corticosteroid production increased after NaCl administration over 5 days and returned to the initial values after 15-day administration. On the contrary, pregnenolone and corticosterone production was suppressed after 5-day course of Mifepristone, but significantly increased after Mifepristone administration for 15 days. Intraperitoneal Mifepristone administration almost completely abolished the response of rat adrenal glands with normo- and hyperglycemia to ACTH in vitro; this effect did not depend on the duration of administration.

Different dosages of mifepristone versus enantone to treat uterine fibroids: A multicenter randomized controlled trial.[Pubmed:28207540]

Medicine (Baltimore). 2017 Feb;96(7):e6124.

BACKGROUND: To evaluate the efficacy and safety of 10 mg and 25 mg Mifepristone per day compared with 3.75 mg enantone in treating uterine fibroids. METHODS: This is a Multicenter randomized controlled trial. A total of 501 subjects with symptomatic uterine fibroids were enrolled and randomized into the group of 10mg, 25mg Mifepristone and 3.75 enantone (with 307, 102 and 92 subjects respectively), with 458 subjects completed the treatment. Three months of daily therapy with oral Mifepristone (at a dose of either 10 mg or 25 mg) or once-monthly subcutaneous injections of enantone (at a dose of 3.75 mg) were used. Change in volume of the largest uterine fibroid was the primary efficacy variable, and secondary efficacy variables included changes in anemia and relevant symptom. Safety evaluation included the analyses of adverse events, laboratory values, and relevant endometrial changes. RESULTS: After three months of treatment, the mean volume of the largest leiomyoma was significantly reduced by Mifepristone 10 mg or 25 mg or enantone 3.75 mg (40.27%, 42.59% and 44.49% respectively) (P < 0.0001). Percentage change from baseline in largest leiomyoma volume was not statistically significant among the three groups (P = 0.1057). Most of the patients in all groups experienced amenorrhea after the treatment. There were also significant elevations in red blood cell count, hemoglobin and hematocrit (P < 0.0001), and significant reductions in prevalence of dysmenorrhea, pelvic pressure, non-menstrual abdominal pain (P < 0.0001) in each group, while no significant difference among the three groups.All study medications are well-tolerated, and no serious adverse event was reported. Treatment-related adverse event rate was significantly lower in Mifepristone 10 mg group, compared to Enantone 3.75 mg group (13.59% vs. 32.58%, P = 0.0002). In both Mifepristone groups, estradiol levels were maintained in the premenopausal range, whereas patients in the enantone group had a significant reduction to postmenopausal levels (P < 0.0001). CONCLUSION: 10mg is as effective as 25mg Mifepristone and 3.75 mg enantone with minimal drug-related side effects, and may provide an alternative for clinical application, especially for patient who are in perimenopause with uterine fibroids.

Efficacy and safety of mifepristone-buccal misoprostol for early medical abortion in an Australian clinical setting.[Pubmed:28303569]

Aust N Z J Obstet Gynaecol. 2017 Jun;57(3):366-371.

BACKGROUND: In 2014, a composite pack containing Mifepristone-buccal misoprostol, indicated for use to 63 days gestation replaced the existing regimen for early medical abortion (EMA) in Australia. AIMS: To provide updated efficacy and safety information for the use of Mifepristone-buccal misoprostol for EMA in Australia, and assess the effect of patient age and gestational age on efficacy. MATERIALS AND METHODS: Observational cohort study of 15 008 women attending one of 16 Marie Stopes International clinics in Australia for an EMA (gestational age Mifepristone in-clinic was followed 24-48 h later by 800 mug buccal misoprostol self-administered at home. Method success was defined as complete abortion not requiring surgical intervention. RESULTS: Follow-up information was available for 87.14% (13 078/15 008) of women. Likelihood of follow-up was significantly lower for women from rural or remote locations (adjusted odds ratio, 0.47; P < 0.001). Medical abortion was successful in 95.16% (12 445/13 078) of women with follow-up. Higher patient and gestational ages were associated (P < 0.001) with a slight increase in method failure. There were 674 serious adverse events (5.15%), mainly due to method failure. Infection (15; 0.11%) and haemorrhage (17; 0.13%) were rare. One death was recorded (<0.01%); however, an association between EMA and cause of death, necrotising pneumonia, was not established. CONCLUSION: Mifepristone-buccal misoprostol is an effective and safe alternative to surgical termination of pregnancy up to 63 days gestation.

Chitosan-based nanoparticles for improved anticancer efficacy and bioavailability of mifepristone.[Pubmed:28144535]

Beilstein J Nanotechnol. 2016 Nov 28;7:1861-1870.

In addition to its well-known abortifacient effect, Mifepristone (MIF) has been used as an anticancer drug for various cancers in many studies with an in-depth understanding of the mechanism of action. However, application of MIF is limited by its poor water solubility and low oral bioavailability. In this work, we developed a drug delivery system based on chitosan nanoparticles (CNs) to improve its bioavailability and anticancer activity. The MIF-loaded chitosan nanoparticles (MCNs) were prepared by convenient ionic gelation techniques between chitosan (Cs) and tripolyphosphate (TPP). The preparation conditions, including Cs concentration, TPP concentration, Cs/MIF mass ratio, and pH value of the TPP solution, were optimized to gain better encapsulation efficiency (EE) and drug loading capacity (DL). MCNs prepared with the optimum conditions resulted in spherical particles with an average size of 200 nm. FTIR and XRD spectra verified that MIF was successfully encapsulated in CNs. The EE and DL of MCNs determined by HPLC were 86.6% and 43.3%, respectively. The in vitro release kinetics demonstrated that MIF was released from CNs in a sustained-release manner. Compared with free MIF, MCNs demonstrated increased anticancer activity in several cancer cell lines. Pharmacokinetic studies in male rats that were orally administered MCNs showed a 3.2-fold increase in the area under the curve from 0 to 24 h compared with free MIF. These results demonstrated that MCNs could be developed as a potential delivery system for MIF to improve its anticancer activity and bioavailability.

RU 38486: a potent antiglucocorticoid in vitro and in vivo.[Pubmed:2864478]

J Steroid Biochem. 1985 Sep;23(3):247-51.

The antiglucocorticoid activity of RU 38486, was studied both in vitro and in vivo. In vitro studies, RU 38486 was characterized by a high affinity (3 times higher than that of dexamethasone) for the cytosolic glucocorticoid receptor in rat hepatoma tissue culture (HTC) cells. This high affinity was due to a very low dissociation rate of the complexes formed with the receptor. In whole cells it was a potent full antagonist of dexamethasone-induced tyrosine aminotransferase (TAT) activity: the IC50 was 6-7 times lower than the concentration of the dexamethasone used. It was devoid of any glucocorticoid activity up to a concentration of 10 microM. In in vivo studies using adrenalectomized rats, RU 38486 totally inhibited dexamethasone-induced hepatic tryptophan oxygenase (TO) activity. It is also the first pure antagonist of dexamethasone-induced hepatic TAT. However, doses as high as 5 mg/kg of body weight were required for a 50% inhibition of the effect of dexamethasone at 0.01 mg/kg. RU 38486 did not display any glucocorticoid effect on these two responses up to 50 mg/kg.

Binding of the anti-progestin RU-486 to rat ovary steroid receptors.[Pubmed:6627946]

Contraception. 1983 Jul;28(1):77-85.

RU-486 is a recently synthesized steroid with anti-progesterone and anti-glucocorticoid properties. Its direct anti-progesterone action on the uterus is believed to be the basis for its ability to induce menstruation and early abortion. RU-486 likely antagonizes progesterone action on the uterus progesterone receptor. We have studied the binding of RU-486 to rat ovary steroid receptors in order to learn whether this interesting synthetic compound binds to ovary steroid receptors and thus learn if this antagonist can be used to better define the mechanism(s) of steroid actions on the ovary. Ovaries from estrogen stimulated hypophysectomized immature female rats were homogenized in buffer. The 100,000 x g supernatant was incubated with tritiated steroid agonists (R5020, dexamethasone, or testosterone) alone or with unlabeled steroids including RU-486. Receptor bound, and free steroid, were separated by Sephadex G-200 columns. The relative abilities of the various tested steroids to bind to the rat ovary progesterone receptor were: RU-486 greater than or equal to R5020 greater than progesterone. RU-486 bound to the ovary glucocorticoid receptor with an affinity equal to that of dexamethasone. The affinity of RU-486 for the rat ovary androgen receptor was only about 9% that of testosterone. Thus, RU-486 binds with very high affinity to the rat ovary progesterone and glucocorticoid receptors. This steroid receptor antagonist offers a new tool by which the mechanism(s) of action of these steroids on the ovary can be tested.

Mifepristone is a progesterone receptor (PR) and glucocorticoid receptor (GR) antagonist with IC50s of 0.2 nM and 2.6 nM in in vitro assay.

Mifepristone,84371-65-3,RU 486, RU 38486,Natural Products,Glucocorticoid Receptor, buy Mifepristone , Mifepristone supplier , purchase Mifepristone , Mifepristone cost , Mifepristone manufacturer , order Mifepristone , high purity Mifepristone