Leukocyte transendothelial migration is one of the most important steps in launching an inflammatory immune response and chronic inflammation can lead to devastating diseases. We developed a novel, potent, non-toxic and patentable inhibitor of transendothelial migration of immune cells. In vivo, compound GT73 exhibited significant therapeutic effects in inflammatory bowel disease (IBD)/Crohn’s disease, multiple sclerosis, Non-alcoholic fatty liver disease, and rheumatoid arthritis models. A detailed 28-day GLP toxicity profile of the lead compound in vivo did not reveal any toxic effects. GT73 provides a unique starting point for designing a novel class of leukocyte transmigration blocking agents with broad therapeutic applications in inflammatory and auto-immune pathologies.