Structure–Activity Studies on Bis-Sulfonamide SHIP1 Activators

Shea T. Meyer, Sandra Fernandes, Robert E. Anderson, Angela Pacherille, Bonnie Toms, William G. Kerr, John D. Chisholm

Research output: Contribution to journalArticlepeer-review


The SH2-containing inositol polyphosphate 5-phosphatase 1 (SHIP1) enzyme opposes the activity of PI3K and therefore is of interest in the treatment of inflammatory disorders. Recent results also indicate that SHIP1 promotes phagolysosomal degradation of lipids by microglia, suggesting that the enzyme may be a target for the treatment of Alzheimer’s disease. Therefore, small molecules that increase SHIP1 activity may have benefits in these areas. Recently we discovered a bis-sulfonamide that increases the enzymatic activity of SHIP1. A series of similar SHIP1 activators have been synthesized and evaluated to determine structure–activity relationships and improve in vivo stability. Some new analogs have now been found with improved potency. In addition, both the thiophene and the thiomorpholine in the parent structure can be replaced by groups without a low valent sulfur atom, which provides a way to access activators that are less prone to oxidative degradation.

Original languageEnglish (US)
Article number8048
Issue number24
StatePublished - Dec 2023


  • SHIP1
  • SHIP2
  • activator
  • phosphatase
  • sulfonamide

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry


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