1.MOA of TRPA1 on IBD

TRPA1 channels are involved in the regulation of neuroimmunity and visceral hypersensitivity

TRPA1 is highly expressed in the enteric nervous system (ENS & DRG), intestinal epithelial cells (EC) and enteroendocrine cells (EEC); Abnormal activation of TRPA1 leadsto abnormal secretion of substance P, 5-HT, cholecystokinin CCK, resulting in increased inflammation, abnormal intestinal motility and visceral hypersensitivity
TRPA1 is expressed in intestinal immune cells, such as T cells and macrophages.Activation of TRPA1 affects the activation of these immune cells

2.Highlights

(1) High gastrointestinal distribution, which significantly reduces systemic toxic and side effect

(2) Asset is a specific TRPA1 inhibitor with low risk of off-target effects

(3) Have the potential to alleviate visceral pain due to visceral inflammation in patients with IBD;

(4) Significantly reduce the levels of intestinal mucosal cytokines in colitis mice, which shows comparable activity to Upadacitinib;

(5) Improve the occurrence of diarrhea and hematochezia in TBNS-induced mice in a dose-dependent manner;

(6) Significantly reduce Pathological Score with better efficacy than Upadacitinib in TBNS-induced mice