2. Academic Validation
  3. Synthesis of urea analogues bearing N-alkyl-N'-(thiophen-2-yl) scaffold and evaluation of their innate immune response to toll-like receptors

Synthesis of urea analogues bearing N-alkyl-N'-(thiophen-2-yl) scaffold and evaluation of their innate immune response to toll-like receptors

  • Eur J Med Chem. 2019 May 1:169:42-52. doi: 10.1016/j.ejmech.2019.02.067.
Zhipeng Chen 1,  Xiaohong Cen 1,  Junjie Yang 1,  Zhiman Lin 1,  Meihuan Liu 1,  Kui Cheng 2
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of New Drug Screening and Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 2 Guangdong Provincial Key Laboratory of New Drug Screening and Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: Chengk@smu.edu.cn.
PMID: 30852386 DOI: 10.1016/j.ejmech.2019.02.067
Abstract

Previous high throughput virtual screening of 10 million-compound and following cell based validation led to the discovery of a novel, nonlipopeptide-like chemotype ZINC 6662436, as Toll-like Receptor 2 (TLR2) agonists. In this report, compounds belonging to four areas of structural modification of ZINC6662436 were evaluated for biological activity using human HEK-Blue TLR2 reporter cells, and human THP-1 monocytic cells, yield SMU-C13 as an optimized, direct and high potent (EC50 = 160 nM) agonist of human TLR2. Moreover, preliminary mechanism studies indicated that SMU-C13 through activates TLR1 and TLR2 then stimulates the NF-κB activation to trigger the downstream cytokines, such as TNF-α and secreted Alkaline Phosphatase (SEAP).

Keywords

Inflammatory; Small molecule antagonist; Toll-like receptor 2 (TLR2); Tumor immunity.

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