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.

The AS1411 aptamer was conjugated to the nanoliposomes to target nucleolin, a protein overexpressed in cancer cells...The encapsulation efficiencies were 88.63% (raloxifene), 41.73% (etoricoxib), and 39.26% (naringin) without the aptamer, and 81.99%, 36.66%, and 38.33%, respectively, with the aptamer. The IC50 of the formula for the three co-loaded agents was 167.4 µg/mL for A549 cells and 2.6 µg/mL for MCF-7 cells. Cytotoxicity was further enhanced using their aptamer conjugate, particularly against the MDA-MB-231 cell line.ConclusionThe novel triple-drug-loaded, aptamer-conjugated nanoliposome formula may be a future cancer treatment strategy.

TMX was associated with an increased risk of EC in premenopausal and perimenopausal women (mean relative risk 2.25; standard deviation 0.9) compared to no treatment or treatment with raloxifene or aromatase inhibitors. TMX seems to increase EC risk and significantly increase the risk of gynecological symptoms in premenopausal and perimenopausal women, with risk persisting years following treatment cessation. Healthcare professionals should counsel these women on potential risks and emphasize prompt evaluation of gynecological symptoms.

Overall, our results suggest that PARP-1 should be explored as a potential target in comprehensive therapeutic approaches in ET-resistant BC.

Female Wistar rats orally administered with SRC@LNPs4 (∼10 mg/kg of RLX) exhibited a hike (unpaired t-test, p < 0.05) of 1.87-fold in the AUC0-t of SRC@LNPs4 (43.04 ± 0.50 h·μg/mL) compared to RLX (22.95 ± 4.30 h·μg/mL) Furthermore, the notable changes observed in the pharmacokinetic parameters of SRC@LNPs4 in rats previously injected with cycloheximide (CHX; 3 mg/kg) suggest that the drug is primarily absorbed into systemic circulation through lymphatic uptake. In conclusion, SRC@LNPs4 presents a valuable strategy to augment oral absorption and bioavailability via lymphatic targeting.

In addition, the combination of PDT with NAC resulted in an improved therapeutic outcome in vivo in SKH-1 mice with cSCC photogenerated by chronic exposition to ultraviolet light. In conclusion, the combination of PDT with NAC or raloxifene enhances PDT efficacy by mitigating resistance mechanisms, which can open new avenues for the treatment of cSCC.