Development of novel PP2A activators for use in the treatment of acute myeloid leukaemia

Org Biomol Chem. 2016 May 18;14(20):4605-16. doi: 10.1039/c6ob00556j.


AAL(S), the chiral deoxy analog of the FDA approved drug FTY720, has been shown to inhibit proliferation and apoptosis in several cancer cell lines. It has been suggested that it does this by activating protein phosphatase 2A (PP2A). Here we report the synthesis of new cytotoxic analogs of AAL(S) and the evaluation of their cytotoxicity in two myeloid cell lines, one of which is sensitive to PP2A activation. We show that these analogs activate PP2A in these cells supporting the suggested mechanism for their cytotoxic properties. Our findings identify key structural motifs required for anti-cancer effects.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Drug Design*
  • Enzyme Activation / drug effects
  • Fingolimod Hydrochloride / chemical synthesis*
  • Fingolimod Hydrochloride / chemistry
  • Fingolimod Hydrochloride / pharmacology*
  • Fingolimod Hydrochloride / therapeutic use
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / enzymology
  • Protein Phosphatase 2 / metabolism*


  • Antineoplastic Agents
  • Protein Phosphatase 2
  • Fingolimod Hydrochloride