Selective hormone receptor degrader
PLEASE DON'T TRY THIS AT HOME! This is highly experimental and incredibly dangerous stuff.
Selective hormone receptor degraders are a class of drugs that promote the degradation/breakdown of a particular nuclear receptor. They bind to a receptor and destabilize the protein, causing it to be degraded through the normal protein degradation process. For example, the selective estrogen receptor degrader fulvestrant promotes the breakdown of estrogen receptors.
The use of selective hormone receptor degraders in trans people has not been studied. However, they could presumably be used similar to how antiestrogens and antiandrogens are used today: to prevent feminization or masculinization due to estrogens and androgens, respectively. Additionally, SERM/SERD hybrids such as elacestrant may be useful in combination with an estrogen for people who desire tissue-specific feminization.
Note that the "selective" in selective estrogen/androgen receptor degrader means something different than the "selective" in selective estrogen/androgen receptor modulator. The selectivity of SERDs/SARDs refers to protein-specific selectivity (e.g., degrading estrogen receptors but not mineralocorticoid receptor). The selectivity of SERMs/SARMs refers to tissue-specific selectivity (e.g., acting as an estrogen in bone but an antiestrogen in uterine tissue).
Selective estrogen receptor degraders (SERD)
|Drug||Other names||Tissue selectivity||Crosses blood-brain barrier||Availability|
|Fulvestrant||antagonist in all tissue||?||currently available|
|Elacestrant||RAD-1901||agonist in bone,
antagonist in breast and uterus
|yes||phase II clinical trials|
|Brilanestrant||GDC-0810||antagonist in all tissue||?||discontinued|
Similar to GnRH agonists and antagonists, SERDs that are not tissue selective come with a risk of osteoporosis.
Selective androgen receptor degraders (SARD)
|Dimethylcurcumin||ASC-J9, ASCJ 9||phase II clinical trials|
- Ashton C. Lai and Craig M. Crews. Induced protein degradation: an emerging drug discovery paradigm. Nat Rev Drug Discov. 2017 Feb; 16(2): 101–114. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684876/
- Osborne, Wakeling, Nicholson. Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action. Published online 2004 Mar 5. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750773/
- Fiona Garner, Maysoun Shomali, Dotty Paquin, C. Richard Lyttle, and Gary Hattersley. RAD1901: a novel, orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560273/
- Adis Insight. Brilanestrant - Genentech. http://adisinsight.springer.com/drugs/800037835
- Kuo-Pao Lai, Chiung-Kuei Huang, Yu-Jia Chang, Chin-Ying Chung, Shinichi Yamashita, Lei Li, Soo Ok Lee, Shuyuan Yeh, and Chawnshang Chang. New Therapeutic Approach to Suppress Castration-Resistant Prostate Cancer Using ASC-J9 via Targeting Androgen Receptor in Selective Prostate Cells. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562731/
- Adis Insight. ASCJ 9. http://adisinsight.springer.com/drugs/800028542