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

orally active Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are in ...

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 agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists ...

(SERM) and

selective estrogen receptor degrader A selective estrogen receptor degrader or downregulator (SERD) is a type of drug which binds to the estrogen receptor (ER) and, in the process of doing so, causes the ER to be degraded and thus downregulated. They are used to treat estrogen rece ...

(SERD) that was developed for the treatment of

estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...

-positive

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...

. It was shown to overcome

antiestrogen Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or ...

(

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

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 ex ...

, 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, ...

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 u ...

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

Duke University Duke University is a private research university in Durham, North Carolina. Founded by Methodists and Quakers in the present-day city of Trinity in 1838, the school moved to Durham in 1892. In 1924, tobacco and electric power industrialist Jam ...

Glaxo Wellcome GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...

, and later,

Dupont DuPont de Nemours, Inc., commonly shortened to DuPont, is an American multinational chemical company first formed in 1802 by French-American chemist and industrialist Éleuthère Irénée du Pont de Nemours. The company played a major role in ...

. 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 Brilanestrant (INN) (developmental code names GDC-0810, ARN-810, RG-6046, RO-7056118) is a nonsteroidal combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) that was discovered by Aragon Pharmaceu ...

, a structural analogue of etacstil.

References

{{Estrogen receptor modulators Antiestrogens GSK plc brands Hormonal antineoplastic drugs Selective estrogen receptor degraders Selective estrogen receptor modulators Triphenylethylenes

See also

References