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Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.

Publication ,  Journal Article
Burks, HE; Abrams, T; Kirby, CA; Baird, J; Fekete, A; Hamann, LG; Kim, S; Lombardo, F; Loo, A; Lubicka, D; Macchi, K; McDonnell, DP; Nunez, J ...
Published in: J Med Chem
April 13, 2017

Tetrahydroisoquinoline 40 has been identified as a potent ERα antagonist and selective estrogen receptor degrader (SERD), exhibiting good oral bioavailability, antitumor efficacy, and SERD activity in vivo. We outline the discovery and chemical optimization of the THIQ scaffold leading to THIQ 40 and showcase the racemization of the scaffold, pharmacokinetic studies in preclinical species, and the in vivo efficacy of THIQ 40 in a MCF-7 human breast cancer xenograft model.

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Published In

J Med Chem

DOI

EISSN

1520-4804

Publication Date

April 13, 2017

Volume

60

Issue

7

Start / End Page

2790 / 2818

Location

United States

Related Subject Headings

  • Tetrahydroisoquinolines
  • Proteolysis
  • Molecular Docking Simulation
  • Mice, Inbred C57BL
  • Medicinal & Biomolecular Chemistry
  • MCF-7 Cells
  • Humans
  • Female
  • Estrogen Receptor alpha
  • Drug Discovery
 

Citation

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Burks, H. E., Abrams, T., Kirby, C. A., Baird, J., Fekete, A., Hamann, L. G., … Peukert, S. (2017). Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer. J Med Chem, 60(7), 2790–2818. https://doi.org/10.1021/acs.jmedchem.6b01468
Burks, Heather E., Tinya Abrams, Christina A. Kirby, Jason Baird, Alexander Fekete, Lawrence G. Hamann, Sunkyu Kim, et al. “Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.J Med Chem 60, no. 7 (April 13, 2017): 2790–2818. https://doi.org/10.1021/acs.jmedchem.6b01468.
Burks HE, Abrams T, Kirby CA, Baird J, Fekete A, Hamann LG, et al. Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer. J Med Chem. 2017 Apr 13;60(7):2790–818.
Burks, Heather E., et al. “Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.J Med Chem, vol. 60, no. 7, Apr. 2017, pp. 2790–818. Pubmed, doi:10.1021/acs.jmedchem.6b01468.
Burks HE, Abrams T, Kirby CA, Baird J, Fekete A, Hamann LG, Kim S, Lombardo F, Loo A, Lubicka D, Macchi K, McDonnell DP, Mishina Y, Norris JD, Nunez J, Saran C, Sun Y, Thomsen NM, Wang C, Wang J, Peukert S. Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer. J Med Chem. 2017 Apr 13;60(7):2790–2818.
Journal cover image

Published In

J Med Chem

DOI

EISSN

1520-4804

Publication Date

April 13, 2017

Volume

60

Issue

7

Start / End Page

2790 / 2818

Location

United States

Related Subject Headings

  • Tetrahydroisoquinolines
  • Proteolysis
  • Molecular Docking Simulation
  • Mice, Inbred C57BL
  • Medicinal & Biomolecular Chemistry
  • MCF-7 Cells
  • Humans
  • Female
  • Estrogen Receptor alpha
  • Drug Discovery