mesoprogestin (EVE104) / Evestra - LARVOL DELTA

Exploring New Treatment Strategies for Endometriosis-Narrative Review. (PubMed, Int J Mol Sci) - "The pharmacodynamic profile of Dienogest (DNG) is compared with the experience of using the pure PR antagonist Vilaprisan and the mixed PR agonist/antagonist Asoprisnil to treat endometriosis...Additionally, another SPRM, Ulipristal acetate, has been associated with rare but serious cases of liver injury...The preclinical profile of the new mesoprogestin EC313 has been presented, showing a higher PR agonistic/antagonistic quotient than Asoprisnil, with comparatively elevated anti-endometriotic activity...Based on the preclinical data currently available, the next generation of mesoprogestins warrants further investigation for the treatment of endometriosis and related gynaecological disorders. This prompts consideration of whether there is potential to enhance the effectiveness of drug discovery strategies within this particular pharmacological class."

Journal • Review • Endometriosis • Gynecology • Hepatology • Liver Failure • Pain • Solid Tumor • Uterine Leiomyoma • Women's Health • PGR

Next step in the development of mesoprogestins: the preclinical profile of EC313. (PubMed, Front Endocrinol (Lausanne)) - "This model shows the same features for the termination of pregnancy by antiprogestins such as Mifepristone and Ulipristal acetate (UPA) in humans. For an explanation of these findings, the possibility is discussed that the mixed agonistic/antagonistic feature of EC313 is tissue target-specific based on its super-additive synergism characteristic for active bifunctional agents. In conclusion, the specific pharmacodynamic profile of this compound opens the possibility for the development of a drug with a distinct pharmaco-endocrinological profile against uterine fibroids, endometriosis, and other PR-dependent gynecological diseases."

Journal • Preclinical • Endometriosis • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health • AR • ER

New Generation of Meso and Antiprogestins (SPRMs) into the Osteoporosis Approach. (PubMed, Molecules) - "Knowledge of the biochemical relationships between hormones and RANK/RANKL signaling provides the opportunity to design novel therapeutic agents to inhibit bone loss, based on the anti-RANKL treatment and inhibition of its interaction with the RANK receptor. The new generation of both anti- and mesoprogestins that inhibit the NF-κB-cyclin D1 axis and blocks the binding of RANKL to RANK can be considered as a potential source of new RANK receptor ligands with anti-RANKL function, which may provide a new perspective into osteoporosis treatment itself as well as limit the osteoporosis rise during breast cancer metastasis to the bone."

Journal • Review • Breast Cancer • Oncology • Osteoporosis • Rheumatology • Solid Tumor • CCND1

New Selective Progesterone Receptor Modulators and Their Impact on the RANK/RANKL Complex Activity. (PubMed, Molecules) - "To meet this need, a new class of selective estrogen receptor modulators (SPRMs) with anti- and mesoprogestin function were tested as potential anti-RANK agents. Conducted experiments proved NFkB expression inhibition as well as cyclin D1 expression limitation under asoprisnil and ulipristal treatment. The established paracrine anti-proliferative activity of antiprogestins together with competitive interaction with RANK make this class of compounds attractive for further study in order to deliver more evidence of their anti-RANK activity and potential application in the breast cancer therapy together with its accompanied osteoporosis."

Journal • CCND1 • PGR