Androgen receptor degrader

Not to be confused with Selective androgen receptor modulator.

A (selective) androgen receptor degrader or downregulator (SARD) is a type of drug which interacts with the androgen receptor (AR) such that it causes the AR to be degraded and thus downregulated.[1] They are under investigation for the treatment of prostate cancer and other androgen-dependent conditions.[1]

As of 2017, dimethylcurcumin (ASC-J9), a SARD, is under development for the treatment of acne vulgaris.[2]

In addition, several PROTACs degraders targeting the androgen receptor have been tested in the clinic:

  1. 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.[3]
  2. 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.[4][5]
  3. Gridegalutamide (CC-94676, AR-LDD): Initially developed by Celgene and now under Bristol Myers Squibb (BMS), this AR PROTAC is in phase I clinical trials for patients with metastatic castration-resistant prostate cancer (mCRPC).[4]
  1. ^ a b Lai AC, Crews CM (February 2017). "Induced protein degradation: an emerging drug discovery paradigm". Nature Reviews. Drug Discovery. 16 (2): 101–114. doi:10.1038/nrd.2016.211. PMC 5684876. PMID 27885283.
  2. ^ "ASCJ 9". AdisInsight. Springer Nature Switzerland AG.
  3. ^ Jia X, Han X (February 2023). "Targeting androgen receptor degradation with PROTACs from bench to bedside". Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 158: 114112. doi:10.1016/j.biopha.2022.114112. PMID 36508999.
  4. ^ a b Israel JS, Marcelin LM, Thomas C, Szczyrbová E, Fuessel S, Puhr M, et al. (July 2024). "Emerging frontiers in androgen receptor research for prostate Cancer: insights from the 2nd international androgen receptor Symposium". Journal of Experimental & Clinical Cancer Research : CR. 43 (1): 194. doi:10.1186/s13046-024-03125-5. PMC 11253403. PMID 39014480.
  5. ^ Chen QH, Munoz E, Ashong D (February 2024). "Insight into Recent Advances in Degrading Androgen Receptor for Castration-Resistant Prostate Cancer". Cancers. 16 (3): 663. doi:10.3390/cancers16030663. PMC 10854644. PMID 38339414.