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Updated: Feb 9, 2026

Comet Assay to Quantify DNA Damage in FLT3 Mutant-expressing 32D Cells after Exposure to Type I and Type II FLT3 Inhibitors
04:36

Comet Assay to Quantify DNA Damage in FLT3 Mutant-expressing 32D Cells after Exposure to Type I and Type II FLT3 Inhibitors

Published on: October 17, 2025

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Discovery of the selective and efficacious inhibitors of FLT3 mutations

Yanle Zhi1, Baoquan Li2, Chao Yao2

  • 1School of Sciences, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, PR China.

European Journal of Medicinal Chemistry
|June 13, 2018
PubMed

Insights

A novel compound, designated 50, effectively inhibits Fms-like tyrosine kinase 3 (FLT3) mutations common in acute myeloid leukemia (AML). This potent inhibitor shows promise for AML therapy, demonstrating efficacy against resistant mutants and inducing cancer cell death.

Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Molecular Biology

Background:

  • Fms-like tyrosine kinase 3 (FLT3) mutations are prevalent in acute myeloid leukemia (AML) and represent a key therapeutic target.
  • Existing FLT3 inhibitors face challenges with resistance and selectivity.

Purpose of the Study:

  • To synthesize and identify novel 1-H-pyrazole-3-carboxamide derivatives with improved FLT3 inhibitory potency and selectivity.
  • To evaluate the efficacy of a lead compound against various FLT3 mutants and AML cell lines.

Main Methods:

  • Synthesis of 1-H-pyrazole-3-carboxamide derivatives.
  • In vitro biochemical assays to determine FLT3 inhibitory activity (IC50).
  • Cell-based assays using MV4-11 AML cell line and flow cytometry for apoptosis analysis.

Main Results:

  • Compound 50 identified as a highly potent (IC50 = 0.213 nM) and selective FLT3 inhibitor.
  • Compound 50 demonstrated activity against quizartinib-resistant FLT3 mutants (FLT3-ITD-D835V, FLT3-ITD-F691L).
  • Compound 50 showed efficacy in MV4-11 AML cells (IC50 = 16.1 nM), induced apoptosis, and exhibited enhanced metabolic stability.

Conclusions:

  • Compound 50 is a promising FLT3 inhibitor with potential for AML therapeutic development.
  • Its potency, selectivity, and activity against resistant mutants warrant further investigation.
  • Compound 50 targets FLT3 signaling pathways, leading to apoptosis in AML cells.
Keywords:
AMLAcute myeloidFLT3FMS-Like tyrosine kinase 3 inhibitorsLeukemia

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