3-Ketosteroid Receptor Related Drug Discovery Products

3-Ketosteroid receptors constitute a class of nuclear hormone receptors, specifically belonging to the NR3 category. As steroid hormone receptors, their endogenous agonists can be subdivided into two groups: 3-hydroxysteroids, exemplified by estrone and 17β-estradiol, and 3-ketosteroids, which encompass dihydrotestosterone (DHT), aldosterone, cortisol, corticosterone, progesterone, and testosterone.

Creative Biolabs offers a wide range of 3-Ketosteroid Receptors related assays and products to satisfy the needs of drug discovery:

• 3-Ketosteroid Receptor Assays
• Membrane Protein Tools

Overview of 3-Ketosteroid Receptors

• AR

The androgen receptor (AR), a nuclear receptor of paramount importance, is activated upon the binding of androgenic hormones, including testosterone and dihydrotestosterone (DHT). As an integral constituent of the steroid hormone receptor family, the AR predominantly mediates the physiological consequences of androgens within the organism.

Fig.1 Androgen and AR action. (Tan, 2015)

• NR3C1

The glucocorticoid receptor (GR), encoded by the NR3C1 gene, represents a key nuclear receptor within the steroid hormone receptor family. This receptor chiefly mediates the physiological ramifications of glucocorticoids, a steroid hormone class encompassing cortisol, cortisone, and corticosterone.

Fig.2 GR signaling. (Weikum, 2016)

• NR3C2

The mineralocorticoid receptor (MR), encoded by the NR3C2 gene, is a nuclear receptor belonging to the steroid hormone receptor family. The MR primarily mediates the physiological effects of mineralocorticoids, exemplified by aldosterone. Despite sharing structural and functional similarities with the glucocorticoid receptor (NR3C1), the mineralocorticoid receptor exhibits distinct roles within the organism.

Fig.3 Diagram represents MR activation in macrophages and T cells. (Barrera-Chimal, 2022)

• PGR

The progesterone receptor (PGR), encoded by the PGR gene, constitutes an essential nuclear receptor within the steroid hormone receptor family. Its primary function is to mediate the physiological effects of progesterone, a critical female sex hormone.

Fig.4 The role of progesterone in the development of breast cancer. (Brisken, 2013)

3-Ketosteroid Receptor Drug Discovery

• Prostate Cancer

The androgen receptor (AR) exerts a critical influence on the pathogenesis and evolution of prostate cancer, given the malignancy's marked susceptibility to androgens. As a result, therapeutic strategies targeting the AR have emerged, encompassing anti-androgens and androgen synthesis inhibitors. Anti-androgens hinder androgen binding to the AR, thereby obstructing its activation, while synthesis inhibitors curtail overall androgen levels. These approaches collectively aspire to inhibit AR signaling, consequently mitigating the growth and survival of prostate cancer cells.

• Breast Cancer

Novel insights have unveiled associations between androgen receptors and specific breast cancer subtypes, notably the luminal androgen receptor (LAR) subtype of triple-negative breast cancer (TNBC). Advancements in selective AR modulators (SARMs) and other AR-targeting therapeutics may yield unprecedented treatment alternatives for patients affected by these breast cancer subtypes.

• Glucocorticoid Receptor in Cancer

Glucocorticoid receptors have been implicated in a diverse array of cancers, spanning leukemia, lymphoma, and select solid tumors. In certain instances, GR activation engenders chemoresistance, thereby exacerbating treatment complexities. The development of selective GR modulators (SGRMs) or the utilization of GR antagonists may proffer innovative strategies for surmounting chemoresistance and augmenting the potency of extant chemotherapy regimens.

• Autoimmune and Inflammatory Diseases

Glucocorticoids, as efficacious anti-inflammatory and immunosuppressive agents, exert their activity through the mediation of the glucocorticoid receptor. Synthetic glucocorticoids have been extensively employed in the management of autoimmune and inflammatory diseases, including asthma, rheumatoid arthritis, and lupus.

References

1. Tan, M.H.; et al. Androgen receptor: structure, role in prostate cancer and drug discovery. Acta Pharmacologica Sinica. 2015, 36(1): 3-23.
2. Weikum, E.R.; et al. Glucocorticoid receptor control of transcription: precision and plasticity via allostery. Nature Reviews Molecular Cell Biology. 2016, 18(3): 159-174.
3. Barrera-Chimal, J.; et al. Mineralocorticoid receptor antagonists in diabetic kidney disease - mechanistic and therapeutic effects. Nature Reviews Nephrology. 2022, 18(1): 56-70.
4. Brisken, C. Progesterone signaling in breast cancer: a neglected hormone coming into the limelight. Nature Reviews Cancer. 2013, 13(6): 385-396.