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Chemical compound
Pharmaceutical compound
Ralaniten acetate (developmental code name EPI-506) is a first-in-class antiandrogen that targets the N-terminal domain (NTD) of the androgen receptor (AR) developed by ESSA Pharmaceuticals and was under investigation for the treatment of prostate cancer.[1][2] This mechanism of action is believed to allow the drug to block signaling from the AR and its splice variants.[3][4] EPI-506 is a derivative of bisphenol A[5] and a prodrug of ralaniten (EPI-002), one of the four stereoisomers of EPI-001, and was developed as a successor of EPI-001.[6] The drug reached phase I/II prior to the discontinuation of its development.[1] It showed signs of efficacy in the form of prostatic specific antigen (PSA) decreases (4–29%) predominantly at higher doses (≥1,280 mg) in some patients but also caused side effects and was discontinued by its developer in favor of next-generation AR NTD inhibitors with improved potency and tolerability.[7]
See also
References
- ^ a b "Ralaniten acetate - ESSA Pharma". AdisInsight. Springer Nature Switzerland AG.
- ^ Martinez-Ariza G, Hulme C (2015). "Recent advances in allosteric androgen receptor inhibitors for the potential treatment of castration-resistant prostate cancer". Pharmaceutical Patent Analyst. 4 (5): 387–402. doi:10.4155/ppa.15.20. PMID 26389532.
- ^ "A phase 1/2 open-label study of safety and antitumor activity of EPI-506, a novel AR N-terminal domain inhibitor, in men with metastatic castration-resistant prostate cancer (mCRPC) with progression after enzalutamide or abiraterone". Journal of Clinical Oncology. ISSN 0732-183X. Archived from the original on 2016-03-06. Retrieved 2016-02-27.
- ^ Silberstein JL, Taylor MN, Antonarakis ES (April 2016). "Novel Insights into Molecular Indicators of Response and Resistance to Modern Androgen-Axis Therapies in Prostate Cancer". Current Urology Reports. 17 (4): 29. doi:10.1007/s11934-016-0584-4. PMC 4888068. PMID 26902623.
- ^ Monaghan AE, McEwan IJ (2016). "A sting in the tail: the N-terminal domain of the androgen receptor as a drug target". Asian Journal of Andrology. 18 (5): 687–94. doi:10.4103/1008-682X.181081. PMC 5000789. PMID 27212126.
- ^ Myung JK, Banuelos CA, Fernandez JG, Mawji NR, Wang J, Tien AH, et al. (July 2013). "An androgen receptor N-terminal domain antagonist for treating prostate cancer". The Journal of Clinical Investigation. 123 (7): 2948–60. doi:10.1172/JCI66398. PMC 3696543. PMID 23722902.
- ^ "ESSA Pharma Announces Results from the Phase 1 Clinical Trial of EPI-506 for Treatment of mCRPC and Updates Clinical and Strategic Plans" (Press release). ESSA Pharma.
External links
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Androgens
(incl. AASTooltip anabolic–androgenic steroid) | |
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| Antiandrogens | | ARTooltip Androgen receptor antagonists | |
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Steroidogenesis
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| Antigonadotropins |
- D2 receptor antagonists (prolactin releasers) (e.g., domperidone, metoclopramide, risperidone, haloperidol, chlorpromazine, sulpiride)
- Estrogens (e.g., bifluranol, diethylstilbestrol, estradiol, estradiol esters, ethinylestradiol, ethinylestradiol sulfonate, paroxypropione)
- GnRH agonists (e.g., leuprorelin)
- GnRH antagonists (e.g., cetrorelix)
- Progestogens (incl., chlormadinone acetate, cyproterone acetate, hydroxyprogesterone caproate, gestonorone caproate, medroxyprogesterone acetate, megestrol acetate)
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