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Tamoxifen-like drug suggests new ways to selectively block estrogen

nding suggests "we could move beyond 'designer estrogens,' to all sorts of small molecules that mimic the actions of various hormones," Greene said. "We could create designer androgens for prostate cancer, or designer glucocorticoids to treat inflammation."

Since "the primary regulator of cofactor recruitment is receptor conformation," added study co-author Donald McDonnell of Duke, findings such as this should lead to the emergence of "a new wave of estrogen receptor modulators with improved specificity. We are moving, he said, "very close to the day where a proteomic profile of a tumor will determine the best SERM or SERD or other endocrine therapy that will yield maximal benefit in the clinic."

New tools such as the Advanced Photon Source at Argonne National Laboratories are making this sort of once-grandiose plan more realistic, Greene said. "We used to solve the structures of one or two molecules a year. Now we have 40 to 50 in progress."

GW5638 was developed as a variation on tamoxifen in the early 1990s by co-author Tim Willson and colleagues at what was then Glaxo Wellcome, hence the name GW5638. McDonnell, at Duke, recognized its potential and demonstrated efficacy in animal models of tamoxifen-resistant breast cancer. The drug has completed initial phase I clinical testing and has garnered significant interest from the pharmaceutical industry.


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Source:University of Chicago Medical Center


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