DFD significantly reduced hemorrhage. DFD significantly increased the serum levels of E2 and inhibited CAMs signaling pathway, which was likely to be involved in the mechanism of action of DFD facilitating residual uterine embryo expulsion in the rat model of incomplete abortion.

Additionally, GPD1 was shown to be regulated by GR, with the GR antagonist mifepristone enhancing the anti-tumorigenic effects of GPD1 in CRPC cells. Mechanistically, targeting GPD1 induced the production of sphingosine 1-phosphate (S1P) and enhanced histone acetylation, thereby inducing the transcription of p21 that involved in cell cycle regulation. In conclusion, Glu-sig could serve as a robust and promising tool to improve the clinical outcomes of PCa patients, and modulating the GR/GPD1 axis that promotes tumor growth may be a promising approach for delaying CRPC progression.

P1, N=94, Recruiting, Montefiore Medical Center | Not yet recruiting --> Recruiting

P1, N=20, Recruiting, Nova Southeastern University | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Jul 2024 --> Sep 2025

First, a rat model of RSA was established using hydroxyurea in combination with mifepristone. It was elucidated that all three were involved in the regulation of progesterone levels and immune function. It initially revealed the mechanism of action of YP in enhancing the improvement of RSA, and it provided a theoretical basis for the quality assessment of YP.

The albumin nanoparticles constructed based on SPARC overexpression in macrophages and endometrial cells and albumin biosafety can achieve the targeted therapy of endometriosis by increasing the passive- and active-mediated drug accumulation in ectopic endometrium and remodeling the immune microenvironment based on macrophage regulation. This study has the following implications: i) overcoming the inherent shortcomings of clinical drugs by nanotechnology is an alternative way of developing medication; ii) developing microenvironment modulation strategies based on macrophage regulation for endometriosis management is feasible.

P2, N=34, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Apr 2025 --> Sep 2024 | Trial primary completion date: Apr 2025 --> Sep 2024

P2, N=400, Recruiting, Chelsea and Westminster NHS Foundation Trust | Phase classification: P3 --> P2

Overall, this study found that a high concentration of mifepristone was effective in the suppression of migration and proliferation of oral cancer cells via the inhibition of PI3K-Akt and MAPK signalling pathways. Further investigation is needed to define its impact on epithelial-mesenchymal transition (EMT) markers.

P3, N=168, Recruiting, University of Auckland | Not yet recruiting --> Recruiting

This study proposes a novel regulatory mechanism of GCs and of TNFi mediated by LAG-3 upregulation in synovial monocytes and PBMCs. LAG-3 modulation may be a promising target for development of novel therapies for inflammatory arthritis.

P1, N=94, Not yet recruiting, Montefiore Medical Center

The study did not meet its primary endpoint. While onapristone-XR was well tolerated in all 3 arms, no objective responses were observed.

The in vivo anti-tumor studies further confirmed the enhanced anti-tumor capabilities of Dox@CLGs + Ber/Ru486@CLPs, including smaller tumor volumes, weak collagen deposition, and low expression levels of α-SMA and CD31 proteins, leading to a superior anti-tumor effect. In brief, this combination therapy based on Dox@CLGs and Ber/Ru486@CLPs could effectively inhibit tumor development, which provides a promising approach for the treatment of breast cancer.

At 16:00 every day, mice in the normal group were administrated with an equal volume of distilled water, while those in the model, Shoutai Pills, and dydrogesterone groups were administrated with hydrocortisone solution by gavage for 4 consecutive days...On day 6, mice were administrated with mifepristone by gavage to establish the model of kidney deficiency-induced abortion...Compared with the model group, dydrogesterone and Shoutai Pills reduced the apoptosis rate(P<0.05). In conclusion, Shoutai Pills can reduce the embryo loss rate and protect embryos by promoting aerobic glycolysis at the maternal-fetal interface and inhibiting the apoptosis of trophoblasts in mice.

P1/2, N=65, Completed, Johns Hopkins University | Phase classification: P=N/A --> P1/2

P2, N=34, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025

P3, N=1186, Not yet recruiting, Leiden University Medical Center

P4, N=30, Recruiting, Washington University School of Medicine | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

However, since mifepristone was developed, its application for breast cancer treatment was immediately proposed...The effects of combined treatments of antiprogestins together with other drugs currently used in the clinic, such as tamoxifen, CDK4/CDK6 inhibitors or pembrolizumab in preclinical models is discussed since it is in this scenario that antiprogestins will be probably introduced. Finally, we explain how transcriptomic or proteomic studies, that were carried out in different luminal breast cancer models and in breast cancer samples that responded or were predicted to respond to the antiprogestin therapy, show a decrease in proliferative pathways. Deregulated pathways intrinsic of each model are discussed, as well as how these analyses may contribute to a better understanding of the mechanisms involved.

Phase-specific differential NK cell activity in BRCA1 mutation carriers, either systemically or locally, may favor site-specific pre-invasive carcinogenesis. These cumulative effects across a reproductive lifecycle in high-risk carriers can have a detrimental effect further supporting epidemiological evidence for ovulation inhibition.

P4, N=1000, Recruiting, Corcept Therapeutics | Trial primary completion date: Jan 2024 --> Mar 2024

P=N/A, N=65, Completed, Johns Hopkins University | Recruiting --> Completed | N=150 --> 65

We found that Dagrocorat and the antagonist RU486 both reduced GR interaction with CREB-binding protein (CBP)/p300 and the Mediator complex compared to the full GR agonist Dexamethasone. Chromatin immunoprecipitation assays revealed that these changes in GR interactome were accompanied by reduced GR chromatin occupancy with Dagrocorat and RU486. Our data offer new insights into the role of differential coregulator recruitment in shaping ligand-specific GR-mediated transcriptional responses.

P2, N=29, Active, not recruiting, University of Chicago | N=64 --> 29

P1, N=20, Recruiting, Nova Southeastern University | Trial primary completion date: Dec 2023 --> Jul 2024

We identified three minimal (10-, 11-, 15-nt) regions essential for exon recognition: c.863_877del [ex8, Δ(E8): 75%] and c.1073_1083del and c.1083_1092del [ex10, Δ(E10): 97% and 62%, respectively]..

SCLC can be added to the long list of very advanced cancers that are treatment resistant to standard therapy, but respond well to PR antagonists.

Taken together, our MNO model overcame limitations of previous meningioma models and showed superior resemblance to parental tumors. Thus, our model could facilitate translational research identifying and selecting drugs for meningioma in the era of precision medicine.

A synthetic glucocorticoid (GC), dexamethasone (Dex) has previously been demonstrated to sensitize cancer cells to chemotherapy...These effects were reversed when cells were pre-treated with RU486, a competitive inhibitor of GCs. Moreover, our in vivo findings of subcutaneous tumor model of Balb/C mice for colon cancer revealed a significant decrease in tumor volume as well as considerable enhancement in the survivability of PDT treated tumor-bearing mice when Dex was present in the formulation. A high Bax/Bcl-xL ratio, high p53 expression, enhanced E-cadherin expression and down-regulation of pro-tumorigenic transcription factors NF-κB and c-Myc were found in tumor lysates from mice treated with D1XP-Nap under PDT, indicating GR-mediated sensitization of the tumor to PDT-induced cell death and enhancement of life-span for tumor bearing mice.

BALB/C mice were randomized into blank, control, model, mifepristone, and low-, medium-, and high-dose Tongxie Yaofang groups...Moreover, the treatment caused different degrees of necrosis in the tumor tissues, down-regulated the protein levels of CD206, JAK1, JAK2, JAK3, STAT3, and STAT6, and up-regulated the protein level of CD86. In summary, Tongxie Yaofang can promote the transformation of M2 macrophages to M1 macrophages and change the tumor microenvironment under chronic stress to inhibit the development of colorectal cancer, which may be related to the JAK/STAT signaling pathway.

Our in vitro and in vivo models demonstrated mifepristone's potential to inhibit NSCLC re-proliferation following cisplatin treatment and tumor growth, respectively, via the ISR-mediated cell death pathway. These findings suggest that mifepristone, as an ISR activator, could enhance the efficacy of cisplatin-based therapy for NSCLC, highlighting the potential of drug repositioning in the search for effective chemosensitizers.

The findings indicated that FBLN1 and COL5A1 were the CAF signature genes in CM, which were associated with the progression, treatment, and prognosis of CM. The comprehensive exploration of CAF signature genes is expected to provide new insight for clinical CM therapy.

The methods of treatment include surgical (myomectomy and hysterectomy, embolization of arteries) and therapeutic treatment (ulipristal acetate, leuprolide acetate, cetrorelix, goserelin, mifepristone). Three different nosological forms of the disease associated with driver mutations in the MED12, HMGA2, and FH genes should be considered when developing or prescribing drugs. For example, synthetic inhibitors and vaccines based on matrix metalloproteinases MMP11 and MMP16 are expected to be effective only for the prevention of the occurrence of MED12-dependent nodules.

The increase in progesterone levels was the most significant side effect detected in mifepristone-treated mice after 14 or 21 days of treatment, probably due to an ovarian compensatory effect not observed in postmenopausal patients. We conclude that in future clinical trials using mifepristone, the possibility of lowering the standard daily dose of 200 mg should be considered.

According to these findings, PRs are acting as critical mediators for the neuroprotective properties of P4 on oxidative stress, pro-inflammatory cytokine levels, and neurological outcomes. PRs also play an important role in regulating the PI3K/p-Akt expression and nongenomic function of P4.

As a representative application, we utilized MNOs in drug screening, and mifepristone, an antagonist of progesterone receptor, showed prominent antitumor efficacy in respect to viability, invasiveness, and protein expression. Taken together, our MNO model overcame limitations of previous meningioma models and showed superiority in terms of resemblance with parental tumors. Thus, we expect that our model can facilitate translational research of identifying and selecting drugs for meningioma in the era of precision medicine.

P2, N=11, Terminated, University of Wisconsin, Madison | Trial completion date: Mar 2025 --> May 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2024 --> Apr 2023; funding

P2, N=201, Recruiting, Memorial Sloan Kettering Cancer Center

Animal models have confirmed the growth inhibitory effects of mifepristone on HCC, including changes in the abundance of HSP60 in mitochondria and cytosol, decreased survivin and Ki-67-positive cells, as well as increased cell apoptosis. In conclusion, the inhibition of HCC growth by mifepristone may be achieved by altering the subcellular distribution of HSP60 to enhance the formation of cytosolic GR-HSP60-survivin complexes in the cells, leading to the degradation of survivin.

P4, N=144, Recruiting, KK Women's and Children's Hospital | Not yet recruiting --> Recruiting | Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Aug 2023 --> Aug 2024