Structure-based discovery of a specific TLR1-TLR2 small molecule agonist from the ZINC drug library database

被引：22

作者：

Chen, Zhipeng ^{[1
,2
]}

Cen, Xiaohong ^{[1
,2
]}

Yang, Junjie ^{[1
,2
]}

Tang, Xiaoshan ^{[1
,2
]}

Cui, Kai ^{[3
]}

Cheng, Kui ^{[1
,2
]}

机构：

[1] Southern Med Univ, Sch Pharmaceut Sci, State Key Lab Organ Failure Res, Guangdong Prov Key Lab New Drug Screening, Guangzhou, Guangdong, Peoples R China

[2] Southern Med Univ, Sch Pharmaceut Sci, Guangzhou Key Lab Drug Res Emerging Virus Prevent, Guangzhou, Guangdong, Peoples R China

[3] Southern Med Univ, Nanfang Hosp, Dept Cardiol, Guangzhou, Guangdong, Peoples R China

来源：

CHEMICAL COMMUNICATIONS | 2018年 / 54卷 / 81期

基金：

中国国家自然科学基金;

关键词：

CELLS;

D O I：

10.1039/c8cc06618c

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We report herein the identification of urea structure-like small molecules by structure-based virtual screening of 10.5 million compounds. Based on a variety of HEK-Blue hTLRs reporter cell assay results, we validated a TLR1/2-specific small molecule agonist, ZINC666243 (SMU127), with EC50 of 0.55 +/- 0.01 M. SMU127 stimulates NF-B activation and promotes TNF secretion in human macrophages and mononuclear cells. Moreover, the in vivo assay indicated that SMU127 could inhibit the growth of breast cancer tumors in BABL/c mice. This work has shown for the first time that a small molecule TLR1/2 agonist can inhibit breast cancer in vivo.

引用

页码：11411 / 11414

页数：4

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