2. Academic Validation
  3. New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons

New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons

  • ACS Med Chem Lett. 2018 Jul 5;9(8):803-808. doi: 10.1021/acsmedchemlett.8b00106.
Lucia Wang 1,  Valeria S Guillen 2,  Naina Sharma 2,  Kevin Flessa 1,  Jian Min 2,  Kathryn E Carlson 2,  Weiyi Toy 3,  Sara Braqi 1,  Benita S Katzenellenbogen 2,  John A Katzenellenbogen 2,  Sarat Chandarlapaty 3,  Abhishek Sharma 1
Affiliations

Affiliations

  • 1 Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, New Jersey 07601 United States.
  • 2 Department of Chemistry, Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 United States.
  • 3 Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States.
PMID: 30128071 DOI: 10.1021/acsmedchemlett.8b00106
Abstract

An effective endocrine therapy for breast Cancer is to selectively and effectively degrade the Estrogen Receptor (ER). Up until now, there have been largely only two molecular scaffolds capable of doing this. In this study, we have developed new classes of scaffolds that possess selective Estrogen receptor Degrader (SERD) and ER antagonistic properties. These novel SERDs potently inhibit MCF-7 breast Cancer cell proliferation and the expression of ER target genes, and their efficacy is comparable to Fulvestrant. Unlike Fulvestrant, the modular protein-targeted chimera (PROTAC)-type design of these novel SERDs should allow easy diversification into a library of analogs to further fine-tune their pharmacokinetic properties including oral availability. This work also expands the pool of currently available PROTAC-type scaffolds that could be beneficial for targeted degradation of various Other therapeutically important proteins.

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