2. Academic Validation
  3. The Investigation of Hsp90 C-terminal inhibitors containing Amide bioisosteres

The Investigation of Hsp90 C-terminal inhibitors containing Amide bioisosteres

  • ChemMedChem. 2024 Aug 17:e202400418. doi: 10.1002/cmdc.202400418.
Brian Blagg 1,  Eva Amatya 2,  Chitra Subramanian 3,  Reagan Long 4,  Kelli McNamara 5,  Mark S Cohen 5
Affiliations

Affiliations

  • 1 University of Notre Dame, Chemistry and Biochemistry, 305 McCourtney Hall, 46556, Notre Dame, UNITED STATES OF AMERICA.
  • 2 University of Notre Dame, Chemistry, UNITED STATES OF AMERICA.
  • 3 University of Illinois at Urbana-Champaign, surgery, UNITED STATES OF AMERICA.
  • 4 University of Notre Dame Libraries, chemistry, UNITED STATES OF AMERICA.
  • 5 University of Illinois Urbana-Champaign, surgery, UNITED STATES OF AMERICA.
PMID: 39153203 DOI: 10.1002/cmdc.202400418
Abstract

Heat Shock Protein 90 (HSP90) is responsible for the proper folding and maturation of ~400 client protein substrates, many of which are directly associated with the ten hallmarks of Cancer. HSP90 is a great target for Cancer therapy including melanoma, since HSP90 inhibition can disrupt multiple oncogenic pathways simultaneously. In this study, we report the synthesis and anti-proliferative activity manifested by a series of HSP90 C-terminal inhibitors against mutant BRaf and wild-type BRaf melanoma cells. Furthermore, we explored structure-activity relationships (SAR) for the amide moiety of 6 (B1), a novel HSP90 C-terminal inhibitor via introduction of amide bioisosteres. Compound 6 displayed an IC50 of 1.01 μM, 0.782 μM, 0.607 μM and 1.413 μM against SKMel173, SKMel103, SKMel19 and A375 cells, respectively.

Keywords

BRAF and MEK mutant resistant; C-terminal inhibitors; anti-cancer; heat shock protein 90 (Hsp90); melanoma.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-162900
    Hsp90抑制剂
    HSP
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