Dimethylcurcumin
Dimethylcurcumin (ASC-J9, ASCJ 9) is a selective androgen receptor degrader (SARD). It promotes the degradation of androgen receptors, resulting in decreased expression of androgenic genes.[1]
It has been investigated as a treatment for prostate cancer[2][3][1] and is currently undergoing phase II trials as a topical acne treatment.[4]
Like other SHRDs, the use of dimethylcurcumin for trans people has not been studied. It could potentially be used systemically in place of or in addition to an antiandrogen for demasculinization. As a topical treatment, it could potentially be used for tissue-specific prevention of masculinization, e.g., it could be used alongside testosterone to prevent body or facial hair while still allowing for a masculine fat distribution, increased muscle mass, and voice changes.
Mechanism of action
Dimethylcurcumin has two proposed mechanisms which contribute to its disruption of AR activity:
- It promotes dissociation of the AR-AR dimer from its coregulators ARA55[1] (TGFB1I1) and ARA70[2][1] (NCOA4), which prevents transcription of AR-regulated genes and leads to degradation of AR.[2][1] See diagram on right.
- It improves the susceptibility of the AR to degradation.[2][1]
Dimethylcurcumin is a curcumin analogue,[3] but the latter mechanism of action appears to be unique to dimethylcurcumin[2]:[Supplementary Fig. 1] (however, see Research warning below). Curcumin has been used in traditional medicine as a treatment for hirsutism, an androgen-sensitive condition, but its efficacy has not been extensively studied.[citation needed]
Research warning
Curcumin is well known to yield false positives on bioassays,[5] so results for curcumin analogues based purely on in vitro assays should be treated with scepticism.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Lai, Kuo-Pao, et al. "New therapeutic approach to suppress castration-resistant prostate cancer using ASC-J9 via targeting androgen receptor in selective prostate cells." The American journal of pathology 182.2 (2013): 460-473. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562731/
- ↑ 2.0 2.1 2.2 2.3 2.4 Yang, Zhiming, et al. "ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor." Nature medicine 13.3 (2007): 348. https://doi.org/10.1038/nm1547
- ↑ 3.0 3.1 Shi, Q., CC-Y. Shih, and Kuo Hsiung Lee. "Novel anti-prostate cancer curcumin analogues that enhance androgen receptor degradation activity." Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents) 9.8 (2009): 904-912. https://doi.org/10.2174/187152009789124655
- ↑ AdisInsight. "ASCJ 9." http://adisinsight.springer.com/drugs/800028542
- ↑ Baker, M. "Deceptive curcumin offers cautionary tale for chemists." Nature 541 (09 January 2017): 144-145. https://doi.org/10.1038/541144a