Selective hormone receptor degrader
Highly-Experimental Research 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.[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)
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)
Drug | Other names | Availability |
---|---|---|
Dimethylcurcumin[5] | ASC-J9, ASCJ 9 | phase II clinical trials[6] |
References
- ↑ 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/
- ↑ 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/
- ↑ 3.0 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/
- ↑ 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