Merestinib blocks Mnk kinase activity in acute myeloid leukemia progenitors and exhibits antileukemic effects in vitro and in vivo

Blood. 2016 Jul 21;128(3):410-4. doi: 10.1182/blood-2016-02-698704. Epub 2016 Jun 15.


Mitogen-activated protein kinase interacting protein kinases (Mnks) play important roles in the development and progression of acute myeloid leukemia (AML) by regulating eukaryotic translation initiation factor 4E (eIF4E) activation. Inhibiting Mnk1/2-induced phosphorylation of eIF4E may represent a unique approach for the treatment of AML. We provide evidence for antileukemic effects of merestinib, an orally bioavailable multikinase inhibitor with suppressive effects on Mnk activity. Our studies show that merestinib effectively blocks eIF4E phosphorylation in AML cells and suppresses primitive leukemic progenitors from AML patients in vitro and in an AML xenograft model in vivo. Our findings provide evidence for potent preclinical antileukemic properties of merestinib and support its clinical development for the treatment of patients with AML.

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors*
  • Adenosine Triphosphatases / metabolism
  • Animals
  • Cation Transport Proteins / antagonists & inhibitors*
  • Cation Transport Proteins / metabolism
  • Cell Line, Tumor
  • Copper-Transporting ATPases
  • Enzyme Inhibitors / pharmacology*
  • Eukaryotic Initiation Factor-4E / metabolism
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / enzymology
  • Mice
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / metabolism
  • Xenograft Model Antitumor Assays


  • Cation Transport Proteins
  • Enzyme Inhibitors
  • Eukaryotic Initiation Factor-4E
  • Neoplasm Proteins
  • Adenosine Triphosphatases
  • ATP7A protein, human
  • Copper-Transporting ATPases