Progesterone plays an important role in the female reproductive system. However, there is also evidence that gynecologic disorders/diseases such as uterine fibroids and endometriosis are progesterone-dependent. Steroidal and non-steroidal selective progesterone receptor modulators (SPRMs) have shown potential for the treatment of such diseases. Steroidal SPRMs, including mifepristone and ulipristal acetate, have proven effective in clinical trials. However, several steroidal SPRMs containing a dimethylamino substituent have been associated with elevated liver enzymes in patients. An earlier drug discovery program identified lonaprisan as a highly selective SPRM that did not show drug-related change in liver enzyme activity. Building on data obtained from that work, here we describe the research program that culminated in the discovery of a novel steroidal SPRM, vilaprisan, which combines an extremely high potency with very favorable drug metabolism and pharmacokinetic properties. Vilaprisan has entered clinical development and is currently undergoing phase 3 clinical trials.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282584 | PMC |
| http://dx.doi.org/10.1002/cmdc.201800487 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
()-1-(3-(3-Hydroxy-4-Methoxyphenyl)-1-(3,4,5-Trimethoxyphenyl)allyl)-1-1,2,4-Triazole and Related Compounds: Their Synthesis and Biological Evaluation as Novel Antimitotic Agents Targeting Breast Cancer.
Pharmaceuticals (Basel)
January 2025
School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, D02 PN40 Dublin, Ireland.
The synthesis of ()-1-(1,3-diphenylallyl)-1-1,2,4-triazoles and related compounds as anti-mitotic agents with activity in breast cancer was investigated. These compounds were designed as hybrids of the microtubule-targeting chalcones, indanones, and the aromatase inhibitor letrozole. : A panel of 29 compounds was synthesized and examined by a preliminary screening in estrogen receptor (ER) and progesterone receptor (PR)-positive MCF-7 breast cancer cells together with cell cycle analysis and tubulin polymerization inhibition.
View Article and Find Full Text PDFBest practices for including sex as a variable in appetite research.
Appetite
January 2025
Department of Reproductive Endocrinology, University Hospital of Zurich, 8091, Zurich, Switzerland.
Despite increasing recognition that sex is a critical variable in appetite research, many studies fail to include participants of both sexes, fail to consider reproductive physiology in participant selection, or include both sexes but fail to test for sex differences in outcomes. To help remedy this situation, this article seeks to engender enthusiasm for including sex as a variable in appetite research. We first illustrate some sex differences in healthy and disordered eating, including both male-female differences and differences across the menstrual cycle.
View Article and Find Full Text PDFAggressive angiomyxoma of the vagina: A case report and literature review.
Medicine (Baltimore)
January 2025
Department of Internal Medicine, Division of Hematology and Oncology, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Republic of Korea.
Rationale: Aggressive angiomyxoma (AAM) is an exceptionally rare mesenchymal tumor that predominantly manifests in the female genital organs during the reproductive age. Its rarity alone makes it a fascinating subject for study. The diagnosis of AAM necessitates differentiation from other benign or mesenchymal tumors and can be confirmed through immunohistochemistry (IHC) staining.
View Article and Find Full Text PDFIntegrated analysis of bioinformatics, mendelian randomization, and experimental validation reveals novel diagnostic and therapeutic targets for osteoarthritis: progesterone as a potential therapeutic agent.
J Orthop Surg Res
January 2025
Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Background: Osteoarthritis (OA), characterized by progressive degeneration of cartilage and reactive proliferation of subchondral bone, stands as a prevalent condition in orthopedic clinics. However, the precise mechanisms underlying OA pathogenesis remain inadequately explored.
Methods: In this study, Random Forest (RF), Least Absolute Shrinkage and Selection Operator (LASSO), and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) machine learning techniques were employed to identify hub genes.
Purpose: Uterine leiomyomas (ULMs) are classified into those with and without MED12 mutations (MED12m(+) and MED12m(-), respectively). This study was undertaken to establish a culture system to evaluate the effect of female hormones on the growth of ULM cells in each ULM subtype.
Methods: ULM cells isolated from MED12m(+) or MED12m(-) tissues were cultured in a monolayer for 7 days with four hormone treatments: estrogen (E) and progesterone (P) (E + P), E only (E), P only (P), and medium only (CTRL).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!