Disease relevance of Nafoxidine

• Concentrations of 17 beta-estradiol and nafoxidine that caused increased release of bone resorbing activity by the breast cancer cells caused a four- to fivefold increase in release of prostaglandins of the E series by MCF-7 cells [1].
• When administered at optimum levels (24 mg/kg daily), this A-ring-substituted estrone displayed no toxicity, slight estrogenicity, and an antitumor activity which was comparable to that of tamoxifen and nafoxidine and was surpassed only by ovariectomy or pharmacological doses of 17 beta-estradiol 3-benzoate [2].
• Effect of the anti-estrogen, Nafoxidine, on NZB/W autoimmune disease [3].
• Five daily injections of enclomiphene, zuclomiphene, tamoxifen, nafoxidine, CI 628 or CI 680 (500 micrograms per injection) promote uterine luminal epithelial cell hypertrophy characteristic of exogenous estrogen administration [4].
• Dissociation of uterine eosinophilia and water imbibition from other estrogen-induced responses by nafoxidine pretreatment [5].

High impact information on Nafoxidine

• 17beta-Estradiol (10(-9) M) binding to the 8S binding protein was inhibited by 3,9-diOHDMBA at concentrations similar to those of nafoxidine HCl (1 x 10(-5) M) [6].
• The tumor potentials of five preneoplastic mammary nodule lines were examined in BALB/cCrgl mice treated with either nafoxidine, an estrogen antagonist; 2-bromo-alpha-ergocryptine, a prolactin suppressant; or testosterone [7].
• Animals treated with nafoxidine or estradiol implants showed sustained long-term nuclear retention of estrogen receptor and increased nuclear RNA polymerase activities for up to 72 hr [8].
• On the other hand, both tamoxifen and nafoxidine can translocate the estrogen receptors into the nucleus, but they have only a limited effect on the total number of specific binding sites of estradiol [9].
• The present data show that tamoxifen and nafoxidine compete specifically with estradiol for the estrogen receptor in the fetal uterus of the guinea pig [9].

Chemical compound and disease context of Nafoxidine

• By contrast, neonatal treatments of mice with other antiestrogens, clomiphene and nafoxidine (100 micrograms/day), induced neither permanent chondrification in the pelvis nor expansion of the pubic ligament nor hernia [10].
• Beginning on the day of surgery, animals were injected daily for 5 days with 0.25, 5 or 25 micrograms/100 g body weight of nafoxidine or 5 mg MER-25 and sacrificed on the sixth day following castration [11].
• Controlled clinical trial of L-dopa and nafoxidine in advanced breast cancer: an E.O.R.T.C. study [12].
• The major toxicity observed with hydroxyurea was hematologic, and the major toxic effect of nafoxidine was an ichthyosis-like skin rash [13].
• METHODS--Fifty regularly cycling guinea pigs were divided into five groups (five animals/group), of which three groups received 3 mg/kg body weight Nafoxidine, Centchroman, or Tamoxifen, respectively, on the 1st, 2nd, or 3rd day of pregnancy [14].

Biological context of Nafoxidine

• Crystal and molecular structure of nafoxidine and stereochemical features of anticancer antiestrogens [15].
• This was probably due to differences in kinetics, nafoxidine requiring a longer time to reach equilibrium than the other estrogens [16].
• In contrast, the action of the antiestrogen nafoxidine is not biphasic in MCF-7 cells; it does not induce PgR over a wide dose range and at high doses, the compound inhibits cell growth [17].
• For comparison, tamoxifen and nafoxidine produced IC50 values of 6.7 microM +/- 1.0 and 7.4 microM +/- 1.1, respectively [18].
• The pure antioestrogen ICI 164,384, and nafoxidine (structurally related to tamoxifen) were good inhibitors of iron ion-dependent lipid peroxidation [19].

Anatomical context of Nafoxidine

• Incubation of the cells for 4 to 6 days with the antiestrogen nafoxidine, however, resulted in a dose-dependent reduction in cytosol DNA polymerase activity to one-half that observed in untreated cells [20].
• Concurrent incubation of the HeLa cells and estrogens with the antiestrogen nafoxidine blocked the subsequent increase in adherence [21].
• Acute administration of 17 beta-estradiol or the antiestrogen nafoxidine to immature rats produces quantitatively similar responses in the uterine stroma and myometrium, although the responses to nafoxidine occur at slightly later times [22].
• Triphenylethylenes [Tamoxifen (TAM), TAM metabolites, and nafoxidine] were found to inhibit Ca2+-calmodulin (CaM)-dependent cAMP phosphodiesterase (PDE) activity of the quail oviduct, whereas 17 beta-estradiol was inactive [23].
• By itself, the triarylethylene antiestrogen, nafoxidine, slightly increased hepatocyte 30MDG uptake, while in combination with estrogen, nafoxidine completely blocked the effects of both E2 and 17 alpha-ethynyl estradiol [24].

Associations of Nafoxidine with other chemical compounds

• Female steroid hormones and lipoprotein synthesis in the cockerel: effects of progesterone and nafoxidine on the estrogenic stimulation of very low density lipoproteins (VLDL) synthesis [25].
• E2 treatment led to a substantial induction of cytoplasmic progestin receptors (approximately 2-fold in the HPOA, approximately 4-fold in the pituitary, and approximately 7-fold in the uterus after 48 h), and this process was considerably inhibited by nafoxidine [26].
• Inhibition of volume-regulated anion channels in cultured endothelial cells by the anti-oestrogens clomiphene and nafoxidine [27].
• It is postulated that CI-628 directly affects the uterus to reduce production of oestrogen receptor protein, while nafoxidine affects the development of the uterine phosphogluconate oxidative pathway indirectly through impaired ovarian function [28].
• Vaginal ADL and uterine myometrial involution were also encountered in 35-day-old mice given neonatal injections of 2-200 micrograms Tx, 200 micrograms clomiphene (Clm) and 200 micrograms nafoxidine (Naf), respectively [29].

Gene context of Nafoxidine

• Tamoxifen, clomiphene, nafoxidine and ICI 182,780 significantly inhibited endothelial cell growth stimulated by bFGF and VEGF [30].
• We can postulate that nafoxidine induces an increase in TIMP-1, which has antiangiogenic activity in the late stages of tube formation, independent of its capacity to inhibit MMPs [31].
• Our data indicated that in nafoxidine-treated endothelial cells MMP-2 was activated [31].
• Furthermore, we show that in yeast the antagonistic effects of the antiestrogen nafoxidine arise from a modulation of the synergistic interactions of TAF-1 and TAF-2, and not simply from an inactivation of TAF-2 by antihormone [32].
• There was no significant difference in pituitary content or concentration of GnRH-R at any time between immature rats treated with estradiol and progesterone or nafoxidine and their respective estradiol-treated controls [33].

Analytical, diagnostic and therapeutic context of Nafoxidine

• After treatment with 5 micrograms nafoxidine for 24 h, uterine cytosol contains approximately one half the total number of estrogen receptors originally present in uteri of untreated animals, and uterine nuclei also contain approximately one half the receptors originally present in unstimulated tissue [34].
• 1. We have used the whole-cell patch clamp technique to study the effect of the partial anti-oestrogens clomiphene and nafoxidine, the pure anti-oestrogens ICI 182,780 and RU 58,668 and the oestrogen ss-estradiol, on the volume-regulated anion channel (VRAC) in cultured pulmonary artery endothelial (CPAE) cells [27].
• In a selected group of patients with metastatic breast cancer who had, in the past, undergone adrenalectomy, Nafoxidine therapy produced objective tumor regression in six out of ten patients [35].

References