A (selective) androgen receptor degrader or downregulator (SARD) is a type of

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

which interacts with the

androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in th ...

(AR) such that it causes the AR to be degraded and thus

downregulated In biochemistry, in the biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell decreases the production and quantities of its cellular components, such as RNA a ...

. They are under investigation for the treatment of

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

and other

androgen-dependent condition An androgen-dependent condition, disease, disorder, or syndrome, is a medical condition that is, in part or full, dependent on, or is sensitive to, the presence of androgenic activity in the body. Known androgen-dependent conditions include acne ...

s. As of 2017,

dimethylcurcumin Dimethylcurcumin (development code ASC-J9) is a nonsteroidal antiandrogen and a synthetic compound, synthetic curcuminoid which is under development by AndroScience Corporation as a topical medication for the treatment of acne vulgaris. It has al ...

(ASC-J9), a SARD, is under development for the treatment of

acne vulgaris Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

. In addition, several PROTACs degraders targeting the androgen receptor have been tested in the clinic: # Bavdegalutamide (ARV-110): Developed by Arvinas, this PROTAC is currently in phase 2 clinical trials and has shown encouraging results for patients with metastatic castration-resistant prostate cancer. # Luxdegalutamide (ARV-766) Developed by Arvinas, this second-generation AR PROTAC has advanced to phase II clinical trials. It was designed to overcome some limitations of ARV-110, particularly in targeting the AR L702H mutation. # Gridegalutamide (CC-94676, AR-LDD): Initially developed by

Celgene Celgene Corporation, headquartered in Summit, New Jersey, was a pharmaceutical company that produced cancer and immunology drugs. Its primary products were Revlimid (lenalidomide), which is used in the treatment of multiple myeloma (63% of 2018 r ...

and now under

Bristol Myers Squibb The Bristol-Myers Squibb Company, Trade name, doing business as Bristol Myers Squibb (BMS), is an American multinational pharmaceutical company. Headquartered in Princeton, New Jersey, BMS is one of the world's largest pharmaceutical companies ...

(BMS), this AR PROTAC is in phase I clinical trials for patients with metastatic castration-resistant prostate cancer (mCRPC).

References

Antiandrogens Hormonal antineoplastic drugs {{Antineoplastic-drug-stub

See also

References