Chemistry:Brilanestrant
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| Other names | GDC-0810, ARN-810, RG-6046, RO-7056118 |
| Routes of administration | Oral |
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| Formula | C26H20ClFN2O2 |
| Molar mass | 446.91 g·mol−1 |
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Brilanestrant (INN) (developmental code names GDC-0810, ARN-810, RG-6046, RO-7056118) is a nonsteroidal combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) that was discovered by Aragon Pharmaceuticals and was under development by Genentech for the treatment of locally advanced or metastatic estrogen receptor (ER)-positive breast cancer.[1][2][3][4][5]
Development of brilanestrant was discontinued by Roche in April 2017.[6] It reached phase II clinical trials for the treatment of breast cancer prior to the discontinuation of its development.[2][5]
Mechanism of action
Similarly to tamoxifen, a SERM, brilanestrant shows some capacity to activate the ER in certain contexts and possesses weak estrogenic activity in the rat uterus, and unlike fulvestrant, which is currently the only SERD to have been marketed, brilanestrant is not a steroid and is orally bioavailable and does not need to be administered by intramuscular injection.[3][4] Brilanestrant has been found to be active in tamoxifen- and fulvestrant-resistant in vitro models of human breast cancer.[5][7] Side effects observed in clinical studies of brilanestrant thus far have included diarrhea, nausea, and fatigue of mostly mild-to-moderate severity.[5]
Brilanestrant is a structural analogue of etacstil, an earlier combined SERM and SERD that was abandoned in 2001 for commercial reasons.[8][9][10]
See also
References
- ↑ "Proposed INN: List 115". WHO Drug Information 30 (2): 242–357. 2016. https://www.who.int/medicines/publications/druginformation/LP_115.pdf.
- ↑ 2.0 2.1 "Drug Profile: GDC 0810". AdisInsight. 12 November 2016. http://adisinsight.springer.com/drugs/800037835.
- ↑ 3.0 3.1 "Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts". Journal of Medicinal Chemistry 58 (12): 4888–904. June 2015. doi:10.1021/acs.jmedchem.5b00054. PMID 25879485.
- ↑ 4.0 4.1 "The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer". eLife 5: e15828. July 2016. doi:10.7554/eLife.15828. PMID 27410477.
- ↑ 5.0 5.1 5.2 5.3 "Evaluating an ER Degrader for Breast Cancer". Cancer Discovery 5 (7): OF15. July 2015. doi:10.1158/2159-8290.CD-NB2015-068. PMID 25956960.
- ↑ John Carroll (27 April 2017). "Roche silently whisks away its $1.7B Seragon drug in a Q1 footnote". Endpoints News. https://endpts.com/roche-silently-whisks-away-its-1-7b-seragon-drug-in-a-q1-footnote/.
- ↑ "Optimization of an indazole series of selective estrogen receptor degraders: Tumor regression in a tamoxifen-resistant breast cancer xenograft". Bioorganic & Medicinal Chemistry Letters 25 (22): 5163–7. November 2015. doi:10.1016/j.bmcl.2015.09.074. PMID 26463130.
- ↑ "Evaluation of the pharmacological activities of RAD1901, a selective estrogen receptor degrader". Endocrine-Related Cancer 22 (5): 713–24. 2015. doi:10.1530/ERC-15-0287. PMID 26162914.
- ↑ "Tamoxifen-like drug suggests new ways to selectively block estrogen.". The University of Chicago Medical Center. 12 May 2005. http://www.uchospitals.edu/news/2005/20050512-gw5638.html.
- ↑ "Effects of a new clinically relevant antiestrogen (GW5638) related to tamoxifen on breast and endometrial cancer growth in vivo". Clinical Cancer Research 8 (6): 1995–2001. June 2002. PMID 12060645.
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