Etacstil (developmental code names GW-5638, DPC974) is an orally active, nonsteroidal, combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) that was developed for the treatment of estrogen receptor-positive breast cancer.[1][2][3] 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.[4][5][6][7][8] Etacstil is a tamoxifen derivative and one of the first drugs to overcome tamoxifen-resistance. It is the predecessor of GW-7604,[3][9][10] of which etacstil is a prodrug (GW-7604 being the 4-hydroxy metabolite of etacstil).[11] This is analogous to the case of tamoxifen being a prodrug of afimoxifene (4-hydroxytamoxifen).[11]
Identifiers | |
---|---|
| |
CAS Number |
|
PubChem CID |
|
ChemSpider |
|
UNII |
|
ChEMBL |
|
Chemical and physical data | |
Formula | C25H22O2 |
Molar mass | 354.449 g·mol−1 |
3D model (JSmol) |
|
| |
|
Etacstil was developed in the early 1990s by Duke University, Glaxo Wellcome, and later, Dupont.[12][13] 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.[6][9][12]
After many dormant years, a recent resurgence of interest in SERDs has led to the development of brilanestrant, a structural analogue of etacstil.[9]