HDL-16 is a highly effective P2Y14R antagonist with anti-colitis effects, targeting P2Y14R in intestinal epithelial cells to alleviate ulcerative colitis.

P2Y14R:0.3095 nM

HDL-16 is a potent P2Y14R antagonist with an IC50 of 0.3095 nM. HDL-16 forms hydrogen bonds with Tyr102 residues through the N atom on its benzooxazole ring and its amine group with His184 residues of P2Y14R. At a concentration of 10μM, HDL-16 showed very low cytotoxicity to HT-29 cells. In addition, HDL-16 effectively inhibited HT-29 cells under specific conditions (20ng/mL TNF-α, 20μM z-VAD-fmk and Smac analog BV6, 2μM; Necrotic apoptosis lasting 8 hours).

HDL-16 significantly inhibited colitis symptoms in mice and maintained the integrity of the intestinal barrier in mice . The experimental animal models were 7-8 week-old male WT mice with P2Y 14 R fl/ FLvil-CRE (P2Y 14 R ∆IEC), P2Y 14 R fl/fl Lyz2-cre and C57BL/6 J background . The dose is 10 μM or 20 μM and is administered rectum daily for 6 days. The results showed that the weight loss and disease activity index (DAI) of mice in the high-dose group were significantly lower than those exposed to 3% w/v, 36-50 kDa DSS (7 days after drinking water). High dose improved the inflammatory infiltration and tissue damage induced by DSS, and significantly inhibited the cell necrosis of intestinal epithelial cells in DSS treated mice.[1]