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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

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

Author(s): Man Zhu, Yanhong Liu, Panpan Lei, Xianpeng Shi, Wenjuan Tang, Xiaoyue Huang, Xiaoyan Pan, Cheng Wang and Weina Ma*

Volume 22, Issue 4, 2022

Published on: 10 March, 2022

Page: [328 - 339] Pages: 12

DOI: 10.2174/1568009622666220225121009

Price: $65

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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, ND-16, JAK2, growth, novel compound, apoptosis.

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