Abstract
Background: 2-Methoxystypandrone (2-MS), isolated from the roots of Polygonum cuspidatum, is a potent dual inhibitor of the STAT3 and NF-κB pathways.
Objective: To investigate the molecular targets and mechanisms of 2-MS.
Method: A biotin-conjugated 2-MS analog, named 2-MS-Biotin, was designed and synthesized. The effects of 2-MS-Biotin on the STAT3 and NF-κB pathways were examined by Western blotting. The cytotoxicity of 2- MS-Biotin was evaluated using real-time cell analysis system. Proteins directly bound to 2-MS-Biotin were pulled down through streptavidin agarose beads and were detected using Western blotting.
Results: 2-MS-Biotin retained the inhibition activities of the parent compound 2-MS on the STAT3 and NF-κB pathways as well as on cancer cell growth. Also, JAK2 and IKK proteins can be effectively pulled down by 2- MS-Biotin.
Conclusion: Using 2-MS-Biotin as a tool, both JAK2 and IKK were identified as the targets of 2-MS.
Keywords: 2-Methoxystypandrone, natural compound, biotin-tagged probe, anticancer drug, JAK2, IKK.
Graphical Abstract
Anti-Cancer Agents in Medicinal Chemistry
Title:Synthesis of Biotinylated 2-methoxystypandrone and Identification of JAK2 and IKK as its Targets
Volume: 18 Issue: 3
Author(s): Shan Kuang, Zhenhua Sima, Jiawei Liu*, Wuguo Li, Qiaoling Song, Qing Zhang and Qiang Yu*
Affiliation:
- Ministry of Education Key Laboratory of Chinese Medicinal Plants Resource from Lingnan, Research Center of Medicinal Plants Resource Science and Engineering, Guangzhou University of Chinese Medicine, Guangzhou,China
- Division of Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai,China
Keywords: 2-Methoxystypandrone, natural compound, biotin-tagged probe, anticancer drug, JAK2, IKK.
Abstract: Background: 2-Methoxystypandrone (2-MS), isolated from the roots of Polygonum cuspidatum, is a potent dual inhibitor of the STAT3 and NF-κB pathways.
Objective: To investigate the molecular targets and mechanisms of 2-MS.
Method: A biotin-conjugated 2-MS analog, named 2-MS-Biotin, was designed and synthesized. The effects of 2-MS-Biotin on the STAT3 and NF-κB pathways were examined by Western blotting. The cytotoxicity of 2- MS-Biotin was evaluated using real-time cell analysis system. Proteins directly bound to 2-MS-Biotin were pulled down through streptavidin agarose beads and were detected using Western blotting.
Results: 2-MS-Biotin retained the inhibition activities of the parent compound 2-MS on the STAT3 and NF-κB pathways as well as on cancer cell growth. Also, JAK2 and IKK proteins can be effectively pulled down by 2- MS-Biotin.
Conclusion: Using 2-MS-Biotin as a tool, both JAK2 and IKK were identified as the targets of 2-MS.
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Cite this article as:
Kuang Shan, Sima Zhenhua, Liu Jiawei*, Li Wuguo, Song Qiaoling, Zhang Qing and Yu Qiang*, Synthesis of Biotinylated 2-methoxystypandrone and Identification of JAK2 and IKK as its Targets, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (3) . https://dx.doi.org/10.2174/1871520617666171106123226
DOI https://dx.doi.org/10.2174/1871520617666171106123226 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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