Leucocyte trans-endothelial migration is one of the most important steps in launching an inflammatory immune response and chronic inflammation. Leucocyte migration inhibitors are considered as promising and potentially effective therapeutic agents to treat inflammatory and auto-immune disorders. We developed a novel molecule methyl 4-((2-(tert-butyl)-6-((2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene) methyl) benzoate, (compound 12 or GT73), that completely blocked leukocyte trans endothelial migration, without any toxic effects on immune or endothelial cells. In vivo, compound 12 exhibited significant therapeutic effects in inflammatory bowel disease (IBD)/Crohn's disease, multiple sclerosis, fatty liver disease, LPS-induced respiratory distress syndrome, lupus and rheumatoid arthritis models. A detailed acute and chronic toxicity profile of the lead compound in vivo did not reveal any toxic effects. such a type of molecule might, therefore provide a unique starting point for designing a novel class of leucocyte transmigration blocking agents with broad therapeutic application in inflammatory and auto immune pathologies. based on this project a start-up company "Alta-Zuz" was established and sold to Maruho, LTD, Osaka, Japan (with the patent licensing). Now the project is in the last steps before the initiation of the clinical trials. We continue to study the lead compound in different autoimmune disease animal model. 

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