Synthesis of Biotinylated 2-methoxystypandrone and Identification of JAK2 and IKK as its Targets

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.

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