Estradiol

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Estradiol

PUBCHEM (5757)

Generally refers to the 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. In humans, it is produced primarily by the cyclic ovaries and the PLACENTA. It is also produced by the adipose tissue of men and postmenopausal women. The 17-alpha-isomer of estradiol binds weakly to estrogen receptors (RECEPTORS, ESTROGEN) and exhibits little estrogenic activity in estrogen-responsive tissues. Various isomers can be synthesized.

Therapeutic Indications

• Menopause
• Osteoporosis

KEGG Database(C00951,D00105) Pathway Androgen and estrogen metabolism Prostate cancer

NEXT BIO Database

Drug Type: Small Molecule; Approved; Investigational

Pharmacology: Estradiol, the principal intracellular human estrogen, is substantially more active than its metabolites, estrone and estriol, at the cellular level.

Mechanism of Action: Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. Indication: For the treatment of urogenital symptoms associated with post-menopausal atrophy of the vagina (such as dryness, burning, pruritus and dyspareunia) and/or the lower urinary tract (urinary urgency and dysuria).

Half Life: 36 hours

Lipinski’s “Rule of Five” Prediction for a Compound’s ABSORPTION OR PERMEABILITY PROPERTIES

Reference Article Ref1 Virtual and biomolecular screening converge on a selective agonist for GPR30

Cristian G Bologa1,7, Chetana M Revankar2,3,7, Susan M Young3, Bruce S Edwards3,4, Jeffrey B Arterburn5, Alexander S Kiselyov6, Matthew A Parker6, Sergey E Tkachenko6, Nikolay P Savchuck6, Larry A Sklar3,4, Tudor I Oprea1 & Eric R Prossnitz2,3

Estrogen is a hormone critical in the development, normal physiology and pathophysiology1 of numerous human tissues2. The effects of estrogen have traditionally been solely ascribed to estrogen receptor alpha (ERalpha) and more recently ERbeta, members of the soluble, nuclear ligand–activated family of transcription factors3. We have recently shown that the seven-transmembrane G protein–coupled receptor GPR30 binds estrogen with high affinity and resides in the endoplasmic reticulum, where it activates multiple intracellular signaling pathways4. To differentiate between the functions of ERalpha or ERbeta and GPR30, we used a combination of virtual and biomolecular screening to isolate compounds that selectively bind to GPR30. Here we describe the identification of the first GPR30-specific agonist, G-1 (1), capable of activating GPR30 in a complex environment of classical and new estrogen receptors. The development of compounds specific to estrogen receptor family members provides the opportunity to increase our understanding of these receptors and their contribution to estrogen biology.

Ref2 Drugs Fut 2006, 31(1): 65 ISSN 0377-8282 Copyright 2006 Prous Science CCC: 0377-8282 DOI: 10.1358/dof.2006.031.01.959122

Structure-function similarity between vitamin D3 and estrogens: Scope for effective drug design for vitamin D3 and estrogen dependent disorders Ray, S., Gupta, A.

Vitamin D3 and estradiol are essential hormones that are formed in the body from the same source cholesterol. Whereas vitamin D3 is required mainly for calcium regulation and bone formation, estradiol regulates the reproductive cycle in women and maintains female characteristics. Both hormones are involved in various other functions in the body and act through their respective receptors which belong to the nuclear receptor superfamily. This article discusses the major role of vitamin D3 and estradiol in disorders such as osteoporosis, cancer and calcium regulation. Their functional similarity may be due to their participation at different junctures of the same mechanistic pathway or else a crosstalk between the two hormones and their opposite receptors. This suggests the possibility of designing effective drugs that would interact with both vitamin D3 and estrogen receptors for the treatment of vitamin D3 and estrogen-dependent disorders.