Rx100

**Rx100** is a first-in-class small molecule analog of lysophosphatidic acid (LPA), designed as a metabolically stable mimic (octadecyl thiophosphate, 18:1δ9) to stimulate LPA receptors. It inhibits activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel by preventing its association with LPA GPCR via the NHERF2 scaffold, reducing CFTR-mediated chloride secretion and fluid loss in secretory diarrhea. Rx100 also enhances intestinal epithelial barrier function by increasing trans-epithelial resistance, reducing paracellular permeability, and maintaining tight junction integrity (e.g., occludin-ZO-1 colocalization). Demonstrated efficacy in mouse models of cholera toxin-induced and *Citrobacter rodentium* infection-induced secretory diarrhea via oral (bioavailability ~80% in rats) and subcutaneous routes, with potential for radioprotection/radiomitigation in the GI tract.