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:Division of Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 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, 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, 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, Division of Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, Division of Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, Division of Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai
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.
