PREP lab medicinal chemistry, led by Dr. Erik Wallén, was able to find completely novel PREP inhibitor structures that lack the structures that were thought to be necessary for PREP inhibitors. However, our oxazole-based compounds turned out to be effective in cellular models of neurodegenerative diseases mechanisms, and had disease-modifying effect on Parkinson's disease mouse models.
Interstingly, the compounds were equally effect as KYP-2047 although they were not as potent PREP inhibitors. It seems that there is a lack of structure-activity relationship between PREP inhibition and effects on mechanisms of neurodegenerative diseases but this is currently under studies. Moreover, the efficacy of the pre-lead compound of oxazoles was equally good as KYP-2047 on alpha-synuclein-based virus vector model of Parkinson's disease, and also in an alpha-synuclein transgenic mouse - having a disease-modifying effect on behavior and alpha-synuclein levels.
The compounds are currently in patenting process, and offer a good possibility for further drug development of PREP inhibitors!