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Bioorg Med Chem Lett. 2017 Apr 15;27(8):1776-1779. doi: 10.1016/j.bmcl.2017.02.060. Epub 2017 Feb 24.

Discovery of new Syk inhibitors through structure-based virtual screening.

Author information

1
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
2
Department of Naval Health Service and Medical Equipment, Faculty of Medicine, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
3
International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
4
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: zhangwnk@hotmail.com.
5
School of Pharmacy, East China University of Science & Technology, 130 Meilong Road, Shanghai 200237, People's Republic of China. Electronic address: jianli@ecust.edu.cn.
6
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: shengcq@hotmail.com.

Abstract

Spleen tyrosine kinase (Syk) is an attractive target for the discovery of new treatments for inflammatory and autoimmune disorders. Structure-based virtual screening was performed for identifying novel scaffolds of Syk inhibitors. A total of 16 hits were discovered in the enzyme assay and 8 compounds had an IC50 value lower than 10μM. In particular, compound 11 (IC50=3.2μM) was active in the cellular Syk assay and could inhibit lymphocytes proliferation in a dose-dependent manner, which could be used as a good starting point for the discovery of new class of Syk inhibitors.

KEYWORDS:

Indazole-3-carboxamide inhibitor; Spleen tyrosine kinase; Virtual screening

PMID:
28268139
DOI:
10.1016/j.bmcl.2017.02.060
[Indexed for MEDLINE]

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