Clinical data
Routes of
Synonyms GDC-0810, ARN-810, RG-6046, RO-7056118
CAS Number 1365888-06-7
PubChem (CID) 56941241
ChemSpider 35308225
Chemical and physical data
Formula C26H20ClFN2O2
Molar mass 446.900603 g/mol
3D model (Jmol) Interactive image

Brilanestrant (INN) (developmental code names GDC-0810, ARN-810, RG-6046, RO-7056118) is a non-steroidal combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) that was discovered by Aragon Pharmaceuticals and is under development by Genentech for the treatment of locally advanced or metastatic estrogen receptor (ER)-positive breast cancer.[1][2][3][4][5] As of September 2016, it is in phase II clinical trials for this indication.[2][5]

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][6] 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.[7][8][9][10]

See also


  2. 1 2
  3. 1 2 Lai, Andiliy; Kahraman, Mehmet; Govek, Steven; Nagasawa, Johnny; Bonnefous, Celine; Julien, Jackie; Douglas, Karensa; Sensintaffar, John; Lu, Nhin; Lee, Kyoung-jin; Aparicio, Anna; Kaufman, Josh; Qian, Jing; Shao, Gang; Prudente, Rene; Moon, Michael J.; Joseph, James D.; Darimont, Beatrice; Brigham, Daniel; Grillot, Kate; Heyman, Richard; Rix, Peter J.; Hager, Jeffrey H.; Smith, Nicholas D. (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): 4888–4904. doi:10.1021/acs.jmedchem.5b00054. ISSN 0022-2623. PMID 25879485.
  4. 1 2 Joseph, James D.; Darimont, Beatrice; Zhou, Wei; Arrazate, Alfonso; Young, Amy; Ingalla, Ellen; Walter, Kimberly; Blake, Robert A.; Nonomiya, Jim; Guan, Zhengyu; Kategaya, Lorna; Govek, Steven P.; Lai, Andiliy G.; Kahraman, Mehmet; Brigham, Dan; Sensintaffar, John; Lu, Nhin; Shao, Gang; Qian, Jing; Grillot, Kate; Moon, Michael; Prudente, Rene; Bischoff, Eric; Lee, Kyoung-Jin; Bonnefous, Celine; Douglas, Karensa L.; Julien, Jackaline D.; Nagasawa, Johnny Y.; Aparicio, Anna; Kaufman, Josh; Haley, Benjamin; Giltnane, Jennifer M.; Wertz, Ingrid E.; Lackner, Mark R.; Nannini, Michelle A.; Sampath, Deepak; Schwarz, Luis; Manning, Henry Charles; Tantawy, Mohammed Noor; Arteaga, Carlos L.; Heyman, Richard A.; Rix, Peter J.; Friedman, Lori; Smith, Nicholas D.; Metcalfe, Ciara; Hager, Jeffrey H. (13 July 2016). "The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer". eLife. 5: e15828. doi:10.7554/eLife.15828. ISSN 2050-084X. PMC 4961458Freely accessible. PMID 27410477.
  5. 1 2 3 4 "Evaluating an ER Degrader for Breast Cancer". Cancer Discovery. 5 (7): OF15–OF15. July 2015. doi:10.1158/2159-8290.CD-NB2015-068. ISSN 2159-8274. PMID 25956960.
  6. Govek, Steven P.; Nagasawa, Johnny Y.; Douglas, Karensa L.; Lai, Andiliy G.; Kahraman, Mehmet; Bonnefous, Celine; Aparicio, Anna M.; Darimont, Beatrice D.; Grillot, Katherine L.; Joseph, James D.; Kaufman, Joshua A.; Lee, Kyoung-Jin; Lu, Nhin; Moon, Michael J.; Prudente, Rene Y.; Sensintaffar, John; Rix, Peter J.; Hager, Jeffrey H.; Smith, Nicholas D. (15 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): 5163–5167. doi:10.1016/j.bmcl.2015.09.074. PMID 26463130.
  7. "Evaluation of the pharmacological activities of RAD1901, a selective estrogen receptor degrader.".
  8. "how breast cancer drugs are developed".
  9. "Tamoxifen-like drug suggests new ways to selectively block estrogen.".
  10. "Effects of a new clinically relevant antiestrogen (GW5638) related to tamoxifen on breast and endometrial cancer growth in vivo.". Clin Cancer Res. 2002. PMID 12060645.

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