Journal article

2-methoxyestradiol and analogs as novel antiproliferative agents: Analysis of three-dimensional quantitative structure-activity relationships for DNA synthesis inhibition and estrogen receptor binding

RA Hughes, T Harris, E Altmann, D McAllister, R Vlahos, A Robertson, M Cushman, ZQ Wang, AG Stewart

MOLECULAR PHARMACOLOGY | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS | Published : 2002

Abstract

2-Methoxyestradiol (2-MEO), a metabolite of estrogen, is an attractive lead compound for the development of novel antitumor and anti-inflammatory agents, because it embodies antiproliferative and antiangiogenic activities in one molecule. However, the affinity of 2-MEO for the estrogen receptor would lead to undesirable side effects. As a prelude to the design of 2-MEO-like compounds with an optimal activity profile, we assayed 2-MEO and a series of analogs for their ability to cause G(1) cell-cycle arrest (by measuring inhibition of DNA synthesis in human cultured airway smooth muscle) and to inhibit binding of [(3)H]estradiol at the estrogen receptor (ER; from rat uterine smooth muscle). O..

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