Related Experiment Video

Updated: Oct 1, 2025

Author Spotlight: Achieving High-Purity In Vitro Differentiation of Th17 Cells Using Cytokine Concentration Modulation
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Author Spotlight: Achieving High-Purity In Vitro Differentiation of Th17 Cells Using Cytokine Concentration Modulation

Published on: October 25, 2024

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Novel Compound, ND-17, Regulates the JAK/STAT, PI3K/AKT, and MAPK Pathways and Restrains Human T-lymphoid Leukemia

Weina Ma1,2, Yanhong Liu1,2, Panpan Lei1,2

  • 1School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, P.R. China.

Current Cancer Drug Targets
|March 7, 2022
PubMed
Abstract

Insights

A novel compound, ND-17, shows significant promise as a Janus kinase 2 (JAK2) inhibitor for treating T cell acute lymphoblastic leukemia (T-ALL). ND-17 effectively suppresses T-ALL cell proliferation by targeting JAK2 signaling pathways.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • T cell acute lymphoblastic leukemia (T-ALL) is a serious hematological malignancy.
  • The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is crucial in T-ALL development.
  • Inhibiting the key molecule JAK2 shows potential for suppressing T-ALL cell proliferation.

Purpose of the Study:

  • To investigate the in vitro anti-tumor effects of a novel nilotinib derivative, ND-17.
  • To explore the interaction of ND-17 with JAK2 in cancer cell lines.

Main Methods:

  • Tetrazolium assay and flow cytometry were used to assess cell proliferation, cell cycle, and apoptosis.
  • Surface plasmon resonance and western blot analyses evaluated ND-17/JAK2 binding interactions.
  • JAK2 knockdown and transfection were performed to understand ND-17's mechanism.

Main Results:

  • ND-17 demonstrated potent inhibition of T-ALL cells, cell cycle arrest at the S phase, and apoptosis induction.
  • ND-17 bound to JAK2's ATP pocket with high affinity, inhibiting JAK2 phosphorylation.
  • ND-17 suppressed multiple signaling pathways including JAK/STAT, PI3K/AKT/mTOR, and MAPK/ERK.

Conclusions:

  • ND-17 exhibits significant anti-tumor activity against T-ALL cells.
  • ND-17 acts as a potent JAK2 inhibitor, offering a potential therapeutic strategy for T-ALL.
  • Further research into ND-17 as a JAK2 inhibitor for T-ALL treatment is warranted.
Keywords:
JAK2MAPK pathwaysND-17T-cell acute lymphoblastic leukemiacell cyclecell growth

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