Etacstil

Nowadays, Etacstil has become a topic of great relevance in today's society. With the advancement of technology and globalization, Etacstil has acquired significant importance in different areas, from politics to economics, science and culture. Throughout history, Etacstil has been the subject of study and debate, generating conflicting opinions and deep reflections on its impact on people's lives. In this article, we will explore different perspectives and approaches on Etacstil, with the aim of offering a comprehensive and enriching vision on a topic that arouses the interest of millions of individuals around the world.

Etacstil
Identifiers
  • (2E)-3-{4-phenyl}acrylic acid
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC25H22O2
Molar mass354.449 g·mol−1
3D model (JSmol)
  • CC/C(=C(\c1ccccc1)/c2ccc(cc2)/C=C/C(=O)O)/c3ccccc3
  • InChI=1S/C25H22O2/c1-2-23(20-9-5-3-6-10-20)25(21-11-7-4-8-12-21)22-16-13-19(14-17-22)15-18-24(26)27/h3-18H,2H2,1H3,(H,26,27)/b18-15+,25-23-
  • Key:HJQQVNIORAQATK-DDJBQNAASA-N

Etacstil (developmental code names GW-5638, DPC974) is an orally active, nonsteroidal, combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) that was developed for the treatment of estrogen receptor-positive breast cancer.[1][2][3] It was shown to overcome antiestrogen (tamoxifen, aromatase inhibitor, fulvestrant) resistance in breast cancer by altering the shape of the estrogen receptor, thus exhibiting SERD properties.[4][5][6][7][8] Etacstil is a tamoxifen derivative and one of the first drugs to overcome tamoxifen-resistance. It is the predecessor of GW-7604,[3][9][10] of which etacstil is a prodrug (GW-7604 being the 4-hydroxy metabolite of etacstil).[11] This is analogous to the case of tamoxifen being a prodrug of afimoxifene (4-hydroxytamoxifen).[11]

Etacstil was developed in the early 1990s by Duke University, Glaxo Wellcome, and later, Dupont.[12][13] In 2001, Bristol Myers-Squibb (BMS) acquired Dupont, and for non-scientific, corporate reasons, closed the trial and abandoned the release of etacstil and its metabolite GW-7604.[6][9][12]

After many dormant years, a recent resurgence of interest in SERDs has led to the development of brilanestrant, a structural analogue of etacstil.[9]

See also

References

  1. ^ Kelloff GJ, Hawk ET, Sigman CC (2008-08-17). Cancer Chemoprevention: Volume 2: Strategies for Cancer Chemoprevention. Springer. ISBN 9781592597680.
  2. ^ "GW 5638 Profile". AdisInsight. Springer Nature Switzerland AG.
  3. ^ a b Becnel LB, Darlington YF, Orechsner S, Easton-Marks J, Watkins CA, McOwiti A, et al. "GW 5638". Nuclear Receptor Signaling Atlas. doi:10.1621/B4A9CIQ78V.
  4. ^ Antiestrogen GW5638 induces a unique structural change in the ER. The biological significance of this conformational change was revealed in studies that demonstrated that tamoxifen-resistant breast tumor explants are not cross-resistant to GW5638. Because of these properties, this drug is currently being developed as a potential therapeutic for tamoxifen-resistant breast cancers.Connor CE, Norris JD, Broadwater G, Willson TM, Gottardis MM, Dewhirst MW, McDonnell DP (April 2001). "Circumventing tamoxifen resistance in breast cancers using antiestrogens that induce unique conformational changes in the estrogen receptor". Cancer Research. 61 (7): 2917–2922. PMID 11306468.
  5. ^ "GW5638 uniquely alters the shape of the estrogen receptor". The Ben May Department for Cancer Research. The University of Chicago. 2015. Archived from the original on 10 October 2015.
  6. ^ a b "Tamoxifen-like drug suggests new ways to selectively block estrogen". The University of Chicago Medical Center. 12 May 2005. Archived from the original on 2018-03-27. Retrieved 2016-10-25.
  7. ^ 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. PMID 12060645.
  8. ^ Tong S, Chen Q, Shan SQ, Dewhirst MW, Yuan F (2006). "Quantitative comparison of the inhibitory effects of GW5638 and tamoxifen on angiogenesis in the cornea pocket assay". Angiogenesis. 9 (2): 53–58. doi:10.1007/s10456-006-9029-x. PMID 16622786. S2CID 35414830.
  9. ^ a b c Wardell SE, Nelson ER, Chao CA, Alley HM, McDonnell DP (October 2015). "Evaluation of the pharmacological activities of RAD1901, a selective estrogen receptor degrader". Endocrine-Related Cancer. 22 (5): 713–724. doi:10.1530/ERC-15-0287. PMC 4545300. PMID 26162914.
  10. ^ Bentrem D, Dardes R, Liu H, MacGregor-Schafer J, Zapf J, Jordan V (February 2001). "Molecular mechanism of action at estrogen receptor alpha of a new clinically relevant antiestrogen (GW7604) related to tamoxifen". Endocrinology. 142 (2): 838–846. doi:10.1210/endo.142.2.7932. PMID 11159857.
  11. ^ a b Bentrem D, Dardes R, Liu H, MacGregor-Schafer J, Zapf J, Jordan V (February 2001). "Molecular mechanism of action at estrogen receptor alpha of a new clinically relevant antiestrogen (GW7604) related to tamoxifen". Endocrinology. 142 (2): 838–846. doi:10.1210/endo.142.2.7932. PMID 11159857.
  12. ^ a b "Osteoporosis Drug Bazedoxifene Stops Growth Of Breast Cancer Cells". Medical News Today. 17 June 2013. Archived from the original on 8 January 2014.
  13. ^ Willson TM, Henke BR, Momtahen TM, Charifson PS, Batchelor KW, Lubahn DB, et al. (May 1994). "3-acrylic acid: a non-steroidal estrogen with functional selectivity for bone over uterus in rats". Journal of Medicinal Chemistry. 37 (11): 1550–1552. doi:10.1021/jm00037a002. PMID 8201587.