Among the most studied SERMs are Tamoxifen and Raloxifene. The pharmacological profile of SERMs therefore reflects a delicate equilibrium between receptor-mediated vascular protection and thrombotic liability. Indeed, their raison d'être increasingly extends beyond oncology into cardiovascular endocrine pharmacology, where they serve as prototypes for designing next-generation agents with optimized receptor selectivity and safer vascular outcomes.

P2, N=100, Completed, Sermonix Pharmaceuticals Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> May 2025 | Trial primary completion date: Dec 2024 --> May 2025

The existing treatments, such as hormonal drugs and selective estrogen receptor modulators like raloxifene, have side effects and recurrence, and thus indicate the need for less harmful non-hormonal therapies...Procyanidin is a phytochemical lead that shows promise for controlling ESR1 signaling in fibroids and endometriosis as a non-hormonal candidate. Procyanidin emerged as a promising in-silico lead for ESR1 modulation, showing high binding affinity and dynamic stability; nevertheless, further pharmacokinetic, ADMET, and experimental validation are required to substantiate its therapeutic potential.

P1, N=40, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Dec 2025

P2, N=242, Recruiting, Beth Israel Deaconess Medical Center | Not yet recruiting --> Recruiting

P1, N=62, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Oct 2026

In this study, we rationally optimized the benzothiophene scaffold of the SERM raloxifene through strategic linker modifications, culminating in the discovery of B7, a potent ERα degrader validated by structure-activity relationship analysis. In the T47D xenograft mouse model, the combination of B7 and Palbociclib demonstrated potent antitumor activity, achieving a tumor growth inhibition rate of 89.2 %. Further structural modification based on B7 may lead to the development of a candidate.

P1/2, N=35, Not yet recruiting, Azure Biotech Inc. | Trial completion date: Dec 2024 --> Jun 2027 | Trial primary completion date: Sep 2024 --> Dec 2026

P2, N=156, Active, not recruiting, Northwestern University | Recruiting --> Active, not recruiting | Trial completion date: Jun 2024 --> Jun 2026 | Trial primary completion date: Jan 2024 --> Jan 2026

This framework invites translational trials using biomarker-enriched patient stratification. If validated, it could reshape the role of sex hormones in male psychiatry-not as contraindications, but as precision neuromodulators aligned with neurobiological pathology.

P4, N=25, Completed, Hospital Clinic of Barcelona | Recruiting --> Completed

Through a signature similarity search using the Library of Integrated Network-Based Cellular Signatures dataset, we identified raloxifene, purpurogallin and enoxacin as pharmacological agents that mimic the effects of CBP20 knockdown. Treatment with these agents significantly inhibited cell growth, highlighting a potential avenue for targeted cancer therapy. These findings suggest that CBP20 plays a pivotal role in RNA modification-mediated tumor progression and may represent a promising therapeutic target in cancer treatment.