A selective estrogen receptor degrader or downregulator (SERD) is a type of drug which binds to the

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 ...

(ER) and, in the process of doing so, causes the ER to be degraded and thus

downregulated In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary proc ...

. They are used to treat estrogen receptor-sensitive or progesterone receptor-sensitive

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 a r ...

, along with older classes of drugs like selective estrogen receptor modulators (SERMs) and

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 ...

s. As of 2016 the only marketed SERD was

fulvestrant Fulvestrant, sold under the brand name Faslodex among others, is a medication used to treat hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression as well as HR-positive, HER2-negative advanced br ...

(brand name Faslodex). As of November 2016 other SERDs under development include brilanestrant and

elacestrant Elacestrant (INN) (developmental code names RAD-1901, ER-306323) is a nonsteroidal combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) (described as a "SERM/SERD hybrid (SSH)") that was discovere ...

. The clinical success of

led to efforts to discover and develop a parallel drug class of

selective androgen receptor degrader A selective androgen receptor degrader or downregulator (SARD) is a type of pharmaceutical drug, drug which interacts with the androgen receptor (AR) such that it causes the AR to be degraded and thus downregulation and upregulation, downregulate ...

s (SARDs).

Investigational

Fulvestrant Fulvestrant, sold under the brand name Faslodex among others, is a medication used to treat hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression as well as HR-positive, HER2-negative advanced br ...

requires large-volume and frequently painful intramuscular injections. In response, pharmaceutical companies are currently developing oral SERDs. Among products in development are: * Giredestrant:

Roche F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX ...

* Amcenestrant (SAR439859):

Sanofi Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...

* AZD9833:

AstraZeneca AstraZeneca plc () is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, England. It has a portfolio of products for major diseases in areas includi ...

* Rintodestrant:

G1 Therapeutics G1 Therapeutics, Inc. is an American biopharmaceutical company headquartered in Research Triangle Park, North Carolina. The company specializes in developing and commercializing small molecule therapeutics for the treatment of patients with cance ...

* LSZ102:

Novartis Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...

* LY3484356:

Eli Lilly Eli Lilly (July 8, 1838 – June 6, 1898) was an American soldier, pharmacist, chemist, and businessman who founded the Eli Lilly and Company pharmaceutical corporation. Lilly enlisted in the Union Army during the American Civil War and ...

Elacestrant Elacestrant (INN) (developmental code names RAD-1901, ER-306323) is a nonsteroidal combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) (described as a "SERM/SERD hybrid (SSH)") that was discovere ...

: Radius Health * ZN-c5: Zentalis *

D-0502 D- means: * Placed before a U.S. state In the United States, a state is a constituent political entity, of which there are 50. Bound together in a political union, each state holds governmental jurisdiction over a separate and defined geogr ...

: Inventisbio * SHR9549: Jiangsu Hengrui Medicine The oral SERDs target ER-positive/HER2-negative

and are tested as monotherapy and in

combination In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are th ...

with other drugs such as the

CDK inhibitor A CDK (cyclin-dependent kinase) inhibitor is any chemical that inhibits the function of CDKs. They are used to treat cancers by preventing overproliferation of cancer cells. The US FDA approved the first drug of this type, palbociclib (Ibrance), ...

palbociclib Palbociclib, sold under the brand name Ibrance among others, is a medication developed by Pfizer for the treatment of HR-positive and HER2-negative breast cancer. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Pa ...

(Ibrance).

References

Antiestrogens Hormonal antineoplastic drugs {{genito-urinary-drug-stub

Investigational

See also

References