Estradiol binding, inhibition

WS-7528 [132147-69-4][VI] a nonsteroidal estrogen, is an isoflavone which has been isolated from Streptomjces sp. No. 7528 and is an estrogen agonist. It inhibits [3ff]-estradiol binding to its receptor in rat uterine cytosol at an inhibitor for 50% of the rats tested (IC q) concentration of 5.7 nM. It also induces the growth of estrogen-dependent human breast cancer cell line MCE-7 (7). 

Bazedoxifene acetate is a third-generation SERM. In in vitro studies bazedoxifene competitively inhibited 17y0-estradiol binding to both ERa (Ki = 0.1 nM) and ER/3 (Ki = 0.03 nM). Bazedoxifene s ability to competitively bind to ERs... 

M10. Markaverich, B. M., and Alejandro, M. A., Type II [3H]estradiol binding site antagonists Inhibition of normal and malignant prostate cell growth and proliferation. Int. J. Oncol. 12, 1127-1135 (1998). 

Note Estradiol, DDD, and related compounds were strong inhibitors of radioactive estradiol to the receptor. IC50 for the inhibition of [3H]17B-estradiol binding to alligator estrogen receptor of several environmental chemicals are given. 

Figure 4. Comparative inhibition of f H]-I7f-estradiol binding to uterine estrogen binding receptors by DMB. (Data are from Reference 18).

SopoM, M. L., BisrvAs, D. K., Sen, K. K., and Talwar, G. P. (1968). The inhibition of bacterial ribonucleic acid polymerase by the estradiol-binding fraction from rat uteri. Arch. Biochem. Biophys. in press. 

Huynh H, Poliak M (1994) Uterotrophic actions of estradiol and tamoxifen are associated with inhibition of uterine insulin-like growth factor binding protein 3 gene expression. Cancer Res 54(12) 3115—3119... 

They have a low incidence of adverse reactions and the reactions that occur are generally mild. Rapid intravenous infusion of H2 antagonists may cause bradycardia. Cimetidine is more inclined to cross the blood-brain barrier and CNS effects such as somnolence and confusion have been described, especially in the elderly and in patients with impaired renal function. Cimetidine in high doses, as the only one of its class, has antiandrogenic effects which could be explained by an increase of prolactin secretion, binding to androgen receptors and inhibition the cytochrome P450 mediated hydroxylation of estradiol. 

Mecfianism of Action A nonsteroidal antiestrogen that competes with estradiol for estrogen-receptor binding sites in the breasts, uterus, and vagina. Therapeutic Effect Inhibits DNAsynthesis and estrogen response. 

Cimetidine inhibits binding of dihydrotestosterone to androgen receptors, inhibits metabolism of estradiol, and increases serum prolactin levels. When used long-term or in high doses, it may cause gynecomastia or impotence in men and galactorrhea in women. These effects are specific to cimetidine and do not occur with the other H2 antagonists. 

Cetrorelix is a synthetic decapeptide that reversibly binds to pituitary GnRH receptors without activating them. Cetrorelix thus inhibits the secretion of FSH and LH in a dose-dependent manner by competing with natural hypothalamic GnRH for pituitary cell surface receptors. At the doses used for in vitro fertilization, cetrorelix produces an immediate suppression of LH this delays the LH surge and thus delays ovulation. At higher doses, cetrorelix also suppresses FSH secretion, thus inhibiting the secretion of estradiol from the ovaries. 

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