ND-16: A Novel Compound for Inhibiting the Growth of Cutaneous T Cell Lymphoma by Targeting JAK2

Curr Cancer Drug Targets. 2022;22(4):328-339. doi: 10.2174/1568009622666220225121009.

Abstract

Objective: Cutaneous T cell lymphoma (CTCL) is a kind of extranodal non-Hodgkin Tcell lymphoma without healable treatment in the clinic. JAK2 amplification in CTCL patients makes it a potential target for CTCL treatment. In the present study, we aimed to evaluate the anticancer effect of ND-16, a novel nilotinib derivate, on CTCL cells and the underlying mechanism targeting JAK2.

Methods and results: We found that ND-16 was capable of regulating JAK2 and had a selective inhibitory effect on CTCL H9 cells. The surface plasmon resonance and molecular docking study indicated ND-16 bound to JAK2 with a high binding affinity. Further investigation revealed that ND-16 inhibited the downstream cascades of JAK2, including STATs, PI3K/AKT/mTOR, and MAPK pathways, followed by regulation of Bcl-2 family members and cell cycle proteins CDK/- Cyclins. Flow cytometry analysis confirmed these results that ND-16-treated H9 cells showed cell apoptosis and cell cycle arrest at S-phase.

Conclusion: ND-16 may be of value in a potential therapy for the management of CTCL.

Keywords: Cutaneous T-cell lymphoma; JAK2; ND-16; apoptosis; growth; novel compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Janus Kinase 2* / antagonists & inhibitors
  • Lymphoma, T-Cell, Cutaneous* / drug therapy
  • Molecular Docking Simulation
  • Pyrimidines* / pharmacology
  • Signal Transduction
  • Skin Neoplasms* / drug therapy

Substances

  • Antineoplastic Agents
  • Pyrimidines
  • JAK2 protein, human
  • Janus Kinase 2
  • nilotinib