Nonpeptidic quinazolinone derivatives as dual nucleotide-binding oligomerization domain-like receptor 1/2 antagonists for adjuvant cancer chemotherapy

  • Eur J Med Chem. 2020 Dec 1;207:112723. doi: 10.1016/j.ejmech.2020.112723.
Yao Ma  1 ,  Jingshu Yang  2 ,  Xiduan Wei  2 ,  Yameng Pei  2 ,  Jingjia Ye  2 ,  Xueyuan Li  2 ,  Guangxu Si  2 ,  Jingyuan Tian  2 ,  Yi Dong  3 ,  Gang Liu  4
Affiliations
  • 1. Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 2A Nanwei Rd, Xicheng Dist, Beijing, 100050, PR China.
  • 2. School of Pharmaceutical Sciences, Tsinghua University, Haidian Dist, Beijing, 100084, PR China.
  • 3. Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 2A Nanwei Rd, Xicheng Dist, Beijing, 100050, PR China. Electronic address: [email protected].
  • 4. School of Pharmaceutical Sciences, Tsinghua University, Haidian Dist, Beijing, 100084, PR China. Electronic address: [email protected].
PMID: 32920426 DOI: 10.1016/j.ejmech.2020.112723
Abstract

Nucleotide-binding oligomerization domain-containing protein 1 and 2 (NOD1/2) receptors are potential immune checkpoints. In this article, a quinazolinone derivative (36b) as a NOD1/2 dual antagonist was identified that significantly sensitizes B16 tumor-bearing mice to paclitaxel treatment by inhibiting both nuclear factor κB (NF-κB) and mitogen-activated protein kinase inflammatory signaling that mediated by NOD1/2.

Keywords
B16 tumor; Dual NOD1/2 antagonists; Quinazolinone; Retroamide.
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