Small molecule targeting of SHIP1 and SHIP2

Biochem Soc Trans. 2020 Feb 28;48(1):291-300. doi: 10.1042/BST20190775.

Abstract

Modulating the activity of the Src Homology 2 (SH2) - containing Inositol 5'-Phosphatase (SHIP) enzyme family with small molecule inhibitors provides a useful and unconventional method of influencing cell signaling in the PI3K pathway. The development of small molecules that selectively target one of the SHIP paralogs (SHIP1 or SHIP2) as well as inhibitors that simultaneously target both enzymes have provided promising data linking the phosphatase activity of the SHIP enzymes to disorders and disease states that are in dire need of new therapeutic targets. These include cancer, immunotherapy, diabetes, obesity, and Alzheimer's disease. In this mini-review, we will provide a brief overview of research in these areas that support targeting SHIP1, SHIP2 or both enzymes for therapeutic purposes.

Keywords: SHIP1; SHIP2; cancer; inhibitors; obesity; small molecule therapeutics.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Animals
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / metabolism
  • Drug Discovery
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Obesity / drug therapy
  • Obesity / metabolism
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / antagonists & inhibitors*
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / chemistry
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / metabolism
  • Small Molecule Libraries / pharmacology*

Substances

  • Small Molecule Libraries
  • INPP5D protein, human
  • INPPL1 protein, human
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases