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. Epub 2020 Aug 14.

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.

MeSH terms

  • Animals
  • Cell Line
  • Drug Discovery
  • Humans
  • Male
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Nod1 Signaling Adaptor Protein / antagonists & inhibitors*
  • Nod1 Signaling Adaptor Protein / metabolism
  • Nod2 Signaling Adaptor Protein / antagonists & inhibitors*
  • Nod2 Signaling Adaptor Protein / metabolism
  • Nucleotides / metabolism
  • Quinazolinones / chemistry*
  • Quinazolinones / pharmacology*

Substances

  • NF-kappa B
  • Nod1 Signaling Adaptor Protein
  • Nod2 Signaling Adaptor Protein
  • Nucleotides
  • Quinazolinones