Etacstil (developmental code names GW-5638, DPC974) is an orally active,

nonsteroidal A nonsteroidal compound is a drug that is not a steroid nor a steroid derivative. Nonsteroidal anti-inflammatory drugs (NSAIDs) are distinguished from corticosteroids as a class of anti-inflammatory agents. List of nonsteroidal steroid receptor mo ...

, combined

selective estrogen receptor modulator Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonists/antagonists (ERAAs), are a class of drugs that act on estrogen receptors (ERs). Compared to pure ER agonists–antagonists (e.g., full agonists and silent ...

(SERM) and selective estrogen receptor degrader (SERD) that was developed for the treatment of

estrogen receptor Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...

-positive

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

. It was shown to overcome antiestrogen (

tamoxifen Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and men. It is also being studied for other types of cancer. It has been used for Albright syndrome ...

aromatase inhibitor Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer in postmenopausal women and in men, and gynecomastia in men. They may also be used off-label to reduce estrogen conversion when supplementing testosterone exo ...

, 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 In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

of etacstil). This is analogous to the case of

being a prodrug of

afimoxifene Afimoxifene, also known as 4-hydroxytamoxifen (4-OHT) and by its tentative brand name TamoGel, is a selective estrogen receptor modulator (SERM) of the triphenylethylene group and an active metabolite of tamoxifen. The drug is under development ...

(4-hydroxytamoxifen). Etacstil was developed in the early 1990s by

Duke University Duke University is a Private university, private research university in Durham, North Carolina, United States. Founded by Methodists and Quakers in the present-day city of Trinity, North Carolina, Trinity in 1838, the school moved to Durham in 1 ...

Glaxo Wellcome GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...

, and later,

Dupont Dupont, DuPont, Du Pont, duPont, or du Pont may refer to: People * Dupont (surname) Dupont, also spelled as DuPont, duPont, Du Pont, or du Pont is a French surname meaning "of the bridge", historically indicating that the holder of the surname re ...

. 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.

References

{{Estrogen receptor modulators Antiestrogens Drugs developed by GSK plc Hormonal antineoplastic drugs Selective estrogen receptor degraders Selective estrogen receptor modulators Triphenylethylenes Carboxylic acids

See also

References