Mike Arnold
Featured Member / Kilo Klub / Verified Sponsor
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Super Raloxifene
(Y-134)
(Y-134)
Hello, everyone. If you haven’t yet heard of the following new S.E.R.M., here’s a little information to familiarize yourself with it.
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Y134, also referred to as Super raloxifene, is a 3rd generation S.E.R.M. with unique benefits for the PED using community. Like its older cousin, raloxifene, Super Raloxifene displays many of the same characteristics, but with greater benefit and apparently, less risk.
More specifically, research shows Super Raloxifene to be more effective at combatting estrogen in breast tissue, making it an attractive compound for the prevention, and likely partial reversal, of gynecomastia.
Super Raloxifene has also, up to this point, been shown to have a significantly greater safety profile than raloxifene. While we don’t yet have human studies demonstrating this, previous research on S.E.R.M.s has often shown similar safety profiles between humans and animals. This includes raloxifene.
When dealing with gynecomastia, many of us have already made the switch from tamoxifen to raloxifene, but with Super Raloxifene (Y134) appearing to possess a more favorable safety profile and greater anti-gynecomastia effects, it may turn out to be the next best SERM for this purpose.
Biological activities of a novel selective oestrogen receptor modulator derived from raloxifene
Abstract
Background and purpose: Selective oestrogen receptor (ER) modulators (SERMs) are of great value in the treatment of breast cancer and osteoporosis. The aim of this study was to characterize pharmacologically a new class of SERMs synthesized based on the core structure of raloxifene.
Experimental approach: Competitive receptor binding and luciferase-based reporter methods were used to study the bioactivities of raloxifene analogues, followed by efficacy determination in breast cancer cell proliferation assay. ER antagonist effects were investigated in female rats by measuring uterine and mammary gland growth, using wet weight, BrdU incorporation and terminal end bud (TEB) as indicators.
Key results: Five analogues, belonging to two different structural series and display higher binding affinities for ERalpha than ERbeta were functionally evaluated. One such analogue, Y134, exhibited potent antagonist activity at ERs in CV-1 cells cotransfected with plasmids containing ERalpha or ERbeta and oestrogen-response element-driven luciferase. The estimated IC(50) value was 0.52 nM for ERalpha and 2.94 nM for ERbeta, comparable to that of raloxifene. Little cytotoxicity was observed at Y134 concentrations below 10 microM. Y134 suppressed oestrogen-stimulated proliferation of ER-positive human breast cancer MCF-7 and T47D cells. At an identical dose, administered to ovariectomized rats, Y134 was more effective than raloxifene at arresting oestrogen-induced outgrowth of TEB and mammary gland DNA synthesis, but their inhibitory effects on the uterus were comparable.
Conclusions and implications: Y134 is a potent ER antagonist with better mammary gland selectivity than raloxifene and shows potential for development as a new SERM for therapeutic use.
LINK: Biological activities of a novel selective oestrogen receptor modulator derived from raloxifene (Y134) - PubMed
Identification of a Raloxifene Analog That Promotes AhR-Mediated Apoptosis in Cancer Cells
Abstract
We previously reported that raloxifene, an estrogen receptor modulator, is also a ligand for the aryl hydrocarbon receptor (AhR). Raloxifene induces apoptosis in estrogen receptor-negative human cancer cells through the AhR. We performed structure–activity studies with seven raloxifene analogs to better understand the structural requirements of raloxifene for induction of AhR-mediated transcriptional activity and apoptosis. We identified Y134 as a raloxifene analog that activates AhR-mediated transcriptional activity and induces apoptosis in MDA-MB-231 human triple negative breast cancer cells. Suppression of AhR expression strongly reduced apoptosis induced by Y134, indicating the requirement of AhR for Y134-induced apoptosis. Y134 also induced apoptosis in hepatoma cells without having an effect on cell cycle regulation. Toxicity testing on zebrafish embryos revealed that Y134 has a significantly better safety profile than raloxifene. Our studies also identified an analog of raloxifene that acts as a partial antagonist of the AhR, and is capable of inhibiting AhR agonist-induced transcriptional activity. We conclude that Y134 is a promising raloxifene analog for further optimization as an anti-cancer agent targeting the AhR.
LINK: Identification of a Raloxifene Analog That Promotes AhR-Mediated Apoptosis in Cancer Cells - PMC
