Selective hormone receptor degrader

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Highly-Experimental Research

PLEASE DON'T TRY THIS AT HOME! This is highly experimental and incredibly dangerous stuff.
Though if you are a professional looking for some new research idea, then by all means you're welcome to use our hypothesis in a study. ❤

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.[1] For example, the selective estrogen receptor degrader fulvestrant promotes the breakdown of estrogen receptors.[1]

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)[edit]

Drug Other names Tissue selectivity Crosses blood-brain barrier Availability
Fulvestrant antagonist in all tissue[2] ? currently available
Elacestrant RAD-1901 agonist in bone,
antagonist in breast and uterus[3]
yes[3] phase II clinical trials
Brilanestrant GDC-0810 antagonist in all tissue ? discontinued[4]

Similar to GnRH agonists and antagonists, SERDs that are not tissue selective come with a risk of osteoporosis.

Selective androgen receptor degraders (SARD)[edit]

Drug Other names Availability
Dimethylcurcumin[5] ASC-J9, ASCJ 9 phase II clinical trials[6]

References[edit]

  1. 1.0 1.1 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/
  2. 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/
  3. 3.0 3.1 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/
  4. Adis Insight. Brilanestrant - Genentech. http://adisinsight.springer.com/drugs/800037835
  5. 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/
  6. Adis Insight. ASCJ 9. http://adisinsight.springer.com/drugs/800028542