Estrogen Receptor Related Drug Discovery Products

Estrogen receptors (ERs) constitute a cadre of intracellular polypeptides that are stimulated by the hormone estrogen (17β-estradiol). These receptors manifest in two distinct isoforms, commonly denoted as α and β, each transcribed from individual genes (ESR1 and ESR2, correspondingly). Upon activation by hormones, estrogen receptors engender dimers, and given that both forms are co-expressed in numerous cellular phenotypes, the resulting receptors may generate ERα (αα) or ERβ (ββ) homodimers or ERαβ (αβ) heterodimers.

Creative Biolabs provides a diverse assortment of Estrogen Receptor assays and products to meet the needs of drug discovery:

• Estrogen Receptor Assays
• Membrane Protein Tools

Overview of Estrogen Receptor

Fig.1 3D renders of ESR1 and ESR2.

• ESR1

The ESR1 gene is responsible for the synthesis of a singular estrogen receptor, functioning as a ligand-activated transcriptional regulator within the nuclear milieu. This receptor exhibits the capacity to establish either homodimeric or heterodimeric assemblages in conjunction with estrogen receptor 2, thereby modulating the transcriptional processes of an array of estrogen-responsive genes implicated in growth, metabolism, sexual maturation, and reproductive phenomena. Additionally, this receptor is expressed in a plethora of non-reproductive tissues and exerts a substantial influence on the development of breast cancer, endometrial cancer, and osteoporosis.

• ESR2

The ESR2 gene engenders a crucial member of the estrogen receptor family, which forms an integral component of the nuclear receptor transcription factor superfamily. The resultant protein possesses an N-terminal domain dedicated to DNA-binding and a C-terminal domain designed for ligand-binding, with localization transpiring within the nuclear, cytoplasmic, and mitochondrial compartments. Upon interaction with 17β-estradiol or cognate ligands, the encoded protein facilitates the formation of homo- or heterodimeric structures, subsequently eliciting transcriptional activation specific to particular DNA sequences.

Estrogen Receptor Drug Discovery

• Breast cancer

Estrogen receptors (ERs) possess paramount significance in both the ontogeny and remediation of breast neoplasms. An estimated 70% of these malignancies exhibit ER-positive phenotypes, characterized by the expression of ERα and reliance on estrogen-mediated signaling for proliferation and sustenance. Pharmacological agents targeting ERs, such as selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs), have been extensively employed in the management of ER-positive breast carcinoma.

Fig.2 Endocrine treatments' mechanisms of action in breast cancer. (Hanker, 2020)

• Endometrial cancer

Additionally, ERs play a pivotal role in the etiopathogenesis of endometrial neoplasms, particularly type 1 endometrial carcinoma, which frequently exhibits hormone dependence. The exploration of SERMs and alternative ER-directed therapeutic interventions hold promise for the treatment of endometrial neoplasms, especially in instances where conventional options prove insufficient or inefficacious.

Fig.3 Endometrial signaling pathways controlled by estrogen receptors. (Yu, 2022)

• Ovarian cancer

Despite the relatively infrequent presence of ER expression in ovarian malignancies compared to breast and endometrial neoplasms, specific subcategories, such as select low-grade serous and endometrioid ovarian carcinomas, demonstrate ER expression. ER-focused treatments may harbor potential as therapeutic modalities for ER-positive ovarian neoplasms.

Fig.4 Estrogen pathways that convert tumor-promoting effects in fallopian tube and ovarian cells. (Mungenast, 2014)

• Prostate cancer

ERβ has been implicated in the genesis and progression of prostatic neoplasms. Current research endeavors seek to ascertain the viability of targeting ERβ, either in isolation or concomitant with supplementary therapies, for the management of advanced or hormone-refractory prostatic carcinoma.

Fig.5 The link between ER and the onset of human prostate cancer and/or BPH (benign prostatic hyperplasia). (Ellem, 2007)

References

1. Hanker, A.B.; et al. Overcoming endocrine resistance in breast cancer. Cancer Cell. 2020, 37(4): 496-513.
2. Yu, K.; et al. Estrogen receptor function: impact on the human endometrium. Frontiers in Endocrinology. 2022, 13: 827724.
3. Mungenast, F.; Thalhammer, T. Estrogen biosynthesis and action in ovarian cancer. Frontiers in Endocrinology. 2014, 5: 192.
4. Ellem, S.J.; Risbridger, G.P. Treating prostate cancer: a rationale for targeting local oestrogens. Nature Reviews Cancer. 2007, 7(8): 621-627.