NOD1/2 antagonist-1

NOD1/2 antagonist-1 (compound 36b) is a potent NOD1/2 (nucleotide-bindingoligomerization domain-like receptor 1/2) dual antagonist, with IC50 values of 1.13 (NOD1) and 0.77 μM (NOD2), respectively. NOD1/2 antagonist-1 has a acceptable T1/2 (67.6 min). NOD1/2 antagonist-1 (compound 36b) can improve the antitumor efficacy of Paclitaxel (PTX)[1].

Research Areas >> Cancer

Signaling Pathways >> Immunology/Inflammation >> NOD-like Receptor (NLR)

Research Areas >> Inflammation/Immunology

NOD1:1.13 μM (IC50)

NOD2:0.77 μM (IC50)

NOD1/2 antagonist-1 (compound 36b) (0-10 μM, 3 h) inhibits C12-iE-DAP-induced or MDP-induced NF-κB activation[1]. NOD1/2 antagonist-1 (0-10 μM, 1 h) suppresses inflammation via NOD1 and NOD2 activation[1]. NOD1/2 antagonist-1 (0-10 μM, 1 h) consistently and dose-dependently reduces the transcription of IL-6, TNF-α and IL-8, respectively[1]. Cell Viability Assay Cell Line: HEK-Blue hNOD1 and HEK-Blue hNOD2 cells[1] Concentration: 0.001, 0.01, 0.1, 1, 10 μM Incubation Time: 3 h Result: Inhibited C12-iE-DAP-induced or MDP-induced NF-κB activation, and had no or little effect on cell growth. Western Blot Analysis Cell Line: THP-1 cells[1] Concentration: 1, 10 μM Incubation Time: 1 h Result: Prevented the increases in p-RIP2, p-IKKα/β, p-p65, p-p38, and p-JNK and the degradation of IκBα in a dose-dependent manner, and blocked NOD1-and NOD2-mediated inflammatory cytokine secretion in THP-1 cells. RT-PCR Cell Line: THP-1 cells[1] Concentration: 1, 10 μM Incubation Time: 1 h Result: Consistently and dose-dependently reduced the transcription of IL-6, TNF-α and IL-8 stimulated by C12-iE-DAP or MDP, respectively.

NOD1/2 antagonist-1 (compound 36b) (50 mg/kg, IV, once every other day, for 16 days) improves the antitumor efficacy of PTX in B16 tumor-bearing model[1]. Animal Model: C57BL/6 mice (6-8 weeks old, male, B16 tumor-bearing model, 4 groups, n = 7 each group)[1] Dosage: 50 mg/kg (36b), 50 mg/kg (36b) + 12 mg/kg (PTX) (formulated in DMSO/Cremophor EL/saline at 5:5:90(v:v:v)) Administration: IV, once every other day (36b), once every 4 days (PTX), for 16 days Result: Significantly reduced tumor growth compared with PTX treatment alone, and the tumor weight inhibitory rate increased from 64.07% to 85.46%.

[1]. Ma Y, Yang J, Wei X, et al. Nonpeptidic quinazolinone derivatives as dual nucleotide-binding oligomerization domain-like receptor 1/2 antagonists for adjuvant cancer chemotherapy. Eur J Med Chem. 2020;207:112723.