NE52-QQ57

NE52-QQ57 is an antagonist of the G protein-coupled receptor 4 (GPR4; IC₅₀ = 0.04 µM).¹ It is selective for GPR4 over human-ether-a-go-go (hERG) and histamine H₃ receptor (IC₅₀s = 19 and >30 µM, respectively). NE52-QQ57 (2 µM) decreases the IL-33-induced increases in IL-17, IFN-γ, TNF-α, NF-κB, matrix metalloproteinase-2 (MMP-2), MMP-9, and COX-2 levels in, and prostaglandin E₂ (PGE₂; Item No. 10410) secretion by, HMC-1 mast cells.² It reduces IL-33-induced increases in mitochondrial reactive oxygen species (ROS) in the same cells. NE52-QQ57 (30 mg/kg twice per day) increases colon length and reduces fecal blood levels and incidence of diarrhea, lymph node volumes, and spleen weight, as well as reduces distal and mid colon inflammation and leukocyte infiltration levels, in a mouse model of ulcerative colitis induced by dextran sodium sulfate (DSS).³ It increases the mechanical paw withdrawal threshold in a rat model of inflammatory pain induced by complete Freud's adjuvant (CFA) when administered at doses of 3, 10, or 30 mg/kg.¹

WARNING This product is not for human or veterinary use.

1. Velcicky, J., Miltz, W., Oberhauser, B., et al. Development of selective, orally active GPR4 antagonists with modulatory effects on nociception, inflammation, and angiogenesis. J. Med. Chem. 60(9), 3672-3683 (2017).

2. Li, J., Chen, K., and Zhao, Z. The protective effects of NE 52-QQ57 against interleukin-33-induced inflammatory response in activated synovial mast cells. J. Biochem. Mol. Toxicol. 36(8), e23116 (2022).

3. Sanderlin, E.J., Marie, M., Velcicky, J., et al. Pharmacological inhibition of GPR4 remediates intestinal inflammation in a mouse colitis model. Eur. J. Pharmacol. 852, 218-230 (2019).