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

• Published in: European journal of medicinal chemistry 2020-12, Vol.207, p.112723-112723, Article 112723
• Main Authors: Ma, Yao, Yang, Jingshu, Wei, Xiduan, Pei, Yameng, Ye, Jingjia, Li, Xueyuan, Si, Guangxu, Tian, Jingyuan, Dong, Yi, Liu, Gang
• Format: Article
• Language: English
• Subjects: Animals; B16 tumor; Cell Line; Drug Discovery; Dual NOD1/2 antagonists; 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; Quinazolinone; Quinazolinones - chemistry; Quinazolinones - pharmacology; Retroamide
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2020.112723

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. [Display omitted] •A new class of quinazolinone derivatives as dual NOD1/2 antagonists was synthesized.•36b exhibited potent inhibitory activity against NOD1/2 with a long T1/2in vitro.•36b sensitized PTX treatment in B16-tumor bearing mice.