Isoliquiritigenin, an Orally Available Natural FLT3 Inhibitor from Licorice, Exhibits Selective Anti-Acute Myeloid Leukemia Efficacy In Vitro and In Vivo

Mol Pharmacol. 2019 Nov;96(5):589-599. doi: 10.1124/mol.119.116129. Epub 2019 Aug 28.


Licorice is a medicinal herb widely used to treat inflammation-related diseases in China. Isoliquiritigenin (ISL) is an important constituent of licorice and possesses multiple bioactivities. In this study, we examined the selective anti-AML (acute myeloid leukemia) property of ISL via targeting FMS-like tyrosine kinase-3 (FLT3), a certified valid target for treating AML. In vitro, ISL potently inhibited FLT3 kinase, with an IC50 value of 115.1 ± 4.2 nM, and selectively inhibited the proliferation of FLT3-internal tandem duplication (FLT3-ITD) or FLT3-ITD/F691L mutant AML cells. Moreover, it showed very weak activity toward other tested cell lines or kinases. Western blot immunoassay revealed that ISL significantly inhibited the activation of FLT3/Erk1/2/signal transducer and activator of transcription 5 (STAT5) signal in AML cells. Meanwhile, a molecular docking study indicated that ISL could stably form aromatic interactions and hydrogen bonds within the kinase domain of FLT3. In vivo, oral administration of ISL significantly inhibited the MV4-11 flank tumor growth and prolonged survival in the bone marrow transplant model via decreasing the expression of Ki67 and inducing apoptosis. Taken together, the present study identified a novel function of ISL as a selective FLT3 inhibitor. ISL could also be a potential natural bioactive compound for treating AML with FLT3-ITD or FLT3-ITD/F691L mutations. Thus, ISL and licorice might possess potential therapeutic effects for treating AML, providing a new strategy for anti-AML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Chalcones / administration & dosage*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / administration & dosage*
  • Female
  • Glycyrrhiza*
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Molecular Docking Simulation / methods
  • Treatment Outcome
  • Xenograft Model Antitumor Assays / methods
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors*
  • fms-Like Tyrosine Kinase 3 / metabolism


  • Chalcones
  • Enzyme Inhibitors
  • isoliquiritigenin
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3