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Development of brilanestrant was discontinued by Roche in April 2017.[6] It reached phase IIclinical trials for the treatment of breast cancer prior to the discontinuation of its development.[2][5]
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Surgery: Introduction to Breast Cancer - Part II
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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 orallybioavailable 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]
^ abLai A, Kahraman M, Govek S, Nagasawa J, Bonnefous C, Julien J, et al. (June 2015). "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. doi:10.1021/acs.jmedchem.5b00054. PMID25879485.
^Govek SP, Nagasawa JY, Douglas KL, Lai AG, Kahraman M, Bonnefous C, et al. (November 2015). "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. doi:10.1016/j.bmcl.2015.09.074. PMID26463130.
^Dardes RC, O'Regan RM, Gajdos C, Robinson SP, Bentrem D, De Los Reyes A, Jordan VC (June 2002). "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. PMID12060645.