Estrogen Receptor/ERR

Tamoxifen is an orally active selective estrogen receptor modulator (SERM) that acts as an estrogen antagonist in breast cells and an agonist in bone, liver, and uterine cells. It can be used to induce gene knockout and liver injury models in mice, and also exhibits multiple biological activities, including activation of Hsp90, induction of autophagy and apoptosis, and inhibition of EBOV and MARV viral infections.

4-Hydroxytamoxifen (ICI 79280) is the active metabolite of Tamoxifen, an estrogen receptor modulator (SERM) with selective and oral potency. 4-Hydroxytamoxifen has antitumor activity and may be used in breast cancer research.

Fulvestrant (ZM 182780) is an estrogen receptor (ER) antagonist (IC50=9.4 nM) and an agonist of GPR30. Fulvestrant has antitumor activity, inhibiting cell proliferation and inducing apoptosis and autophagy.

Vepdegestrant (ARV-471) is an estrogen receptor (ER) α PROTAC molecule that degrades ER in ER-positive breast cancer cell lines with a DC50 of approximately 1 nM. It can reduce the expression of classically regulated ER target genes and inhibit the growth of ER-dependent cell lines (including those expressing ESR1 variants, such as Y537S and D538G) by degrading ER.

SLU-PP-332 is a pan-estrogen receptor-related receptor (ERR) agonist with high affinity for ERRα, ERRβ, and ERRγ, exhibiting EC50 values of 98, 230, and 430 nM, respectively. SLU-PP-332 enhances mitochondrial function and cellular respiration, increases type IIa oxidized skeletal muscle fibers, and enhances exercise tolerance in skeletal muscle cell lines. It has potential applications in the study of metabolic diseases, improvement of muscle function, and amelioration of metabolic disorders and aging.

27-Hydroxycholesterol (25(R)-27-hydroxy Cholesterol) is a selective modulator of estrogen receptor and an agonist of the liver X receptor.

(E/Z)-4-Hydroxytamoxifen (Afimoxifene) is a novel estrogen inhibitor, commonly used in research for various estrogen-dependent conditions, including cyclic mastalgia and gynecomastia.

PHTPP is a selective ERβ antagonist.

Cholesterol is the primary sterol in mammals, accounting for approximately 20–25% of the plasma membrane structure. It plays a key role in regulating membrane fluidity, permeability, and protein function. As an endogenous agonist of estrogen-related receptor α (ERRα), cholesterol is widely involved in metabolic regulation and serves as a precursor for the synthesis of hormones and bile acids. It is commonly used in experimental models of hyperlipidemia.

Saikosaponin D is a novel SERCA inhibitor by inhibiting NF-κB and STAT3 signaling to protect against acetaminophen-induced hepatotoxicity.

Kaempferol (Robigenin) is a natural flavonoid and an inverse agonist of ERRα and ERRγ. Kaempferol has a wide range of antitumor, anti-inflammatory, antioxidant, antibacterial and antiviral activities.

Coumestrol that existed in soybean products suppresses the proliferation of ES2 cells (IC50: 50 μM). It exhibits activities against neurological disorders, cancers and autoimmune diseases.

Indazole-Cl is a selective ERß agonist and a selective estrogen receptor modifier (SERM).

Elacestrant (RAD1901) with IC50s of 48 and 870 nM for ERα and ERβ, respectively.Elacestrant  is an orally available selective estrogen receptor degrader .

Liquiritigenin (4',7-Dihydroxyflavanone), a flavonoid aglycone from licorice, is a highly selective estrogen receptor β (ERβ) agonist.

Estradiol (E2) is a naturally occurring steroidal sex hormone that is essential for female fertility and maintenance of secondary sexual characteristics. Estradiol upregulates IL-6 expression through estrogen receptor beta (ERβ).

Giredestrant (GDC-9545) potently competes with estradiol for binding and induces a conformational change within the ER ligand binding domain. Giredestrant has anti-tumor activity. Giredestrant, a non-steroidal ER ligand, is an orally active and selective estrogen receptor (ER) antagonist.

Bazedoxifene acetate (WAY-TES 424) is a novel selective estrogen receptor modulator (SERM).

G-1 is a nonsteroidal, high-affinity, and selective GPR30 agonist (Ki: 11 nM).

Estrone sulfate sodium (17β-Estrone 3-sulfate) is an endogenous steroid and an estrogen ester that is biologically inactive. It is converted by steroid sulfatase into estrone . Estrone sulfate sodium has been investigated as a ligand for targeting organic anion transporting polypeptides f

Delphinidin chloride, a natural plant pigment found in berries and red wine, is a precursor of certain anthocyanins. Delphinidin chloride induces the release of nitric oxide from the vascular endothelium, resulting in vascular relaxation. At the dose of 1-40 μM, epithelial growth factor receptor signaling and estrogen receptor α expression were inhibited, which was associated with apoptosis and autophagy. Delphinidin chloride regulates JAK/STAT3 and MAPKinase signaling. Delphinidin also inhibited the histone acetyltransferase activity of p300/CBP (IC50 was about 30 μM).

α-Zearalenol is one of the major metabolites of Zearalenone. α-Zearalenol has structural analogy to estrogen, thus α-Zearalenol can bind to estrogen receptors (ERs).

Demethylzeylasteral (T-96), isolated from Tripterygium wilfordii, has anti-inflammatory, immunosuppressive and anti-tumor activities. It inhibits the invasion of triple-negative breast cancer by blocking the TGF-β signaling pathway, and it can significantly reduce atherosclerosis.

GSK5182 is a highly selective inverse estrogen-related receptor γ agonist (IC50 : 79 nM)