|Chemical and physical data|
|Molar mass||354.45 g·mol−1|
|3D model (Jmol)||Interactive image|
Etacstil (developmental code names GW-5638, DPC974) is an orally active, non-steroidal, combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) that was developed for the treatment of estrogen receptor-positive breast cancer. It was shown to overcome antiestrogen (tamoxifen, aromatase inhibitor, fulvestrant) resistance in breast cancer by altering the shape of the estrogen receptor, thus exhibiting SERD properties. Etacstil is a tamoxifen derivative and one of the first drugs to overcome tamoxifen-resistance. It is the predecessor of GW-7604, of which etacstil is a prodrug (GW-7604 being the 4-hydroxy metabolite of etacstil). This is analogous to the case of tamoxifen being a prodrug of afimoxifene (4-hydroxytamoxifen).
Etacstil was developed in the early 1990s by Duke University, Glaxo Wellcome, and later, Dupont. In 2001, Bristol Myers-Squibb (BMS) acquired Dupont, and for non-scientific, corporate reasons, closed the trial and abandoned the release of etacstil and its metabolite GW-7604.
After many dormant years, a recent resurgence of interest in SERDs has led to the development of brilanestrant, a structural analogue of etacstil.
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- Antiestrogen GW5638 induces a unique structural change in the ER. The biological significance of this conformational change was revealed in studies that demonstrated that tamoxifen-resistant breast tumor explants are not cross-resistant to GW5638. Because of these properties, this drug is currently being developed as a potential therapeutic for tamoxifen-resistant breast cancers."Circumventing tamoxifen resistance in breast cancers using antiestrogens that induce unique conformational change in the estrogen receptor.". Cancer Res. 2001. PMID 11306468.
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