Dr. Ben Cravatt	Dr. Gregory Fu

A continent apart, synthetic chemist Dr. Gregory Fu, of MIT, Cambridge, MA and Dr. Ben Cravatt of Scripps, La Jolla, CA formed a productive scientific collaboration after a unique series of chemicals Dr. Fu donated to a public repository was found to inhibit a protein of interest to Dr. Cravatt. Dr. Fu created novel aza-β-lactam (ABL) compounds, relatives of penicillin and other β-lactam antibiotics, and provided them to the Common Fund-supported Molecular Libraries Small Molecule Repository. This public resource contains over 350,000 different chemical compounds that are distributed to a network of centers for screening in high throughput assays submitted by the research community. Using an assay designed by Dr. Cravatt, the Molecular Libraries screening center at Scripps discovered that four of Dr. Fu’s novel ABLs inhibited protein phosphatase methyltransferase-1 (PME-1), a protein that has no previously known inhibitors. In work published in PNAS, the collaborators discovered that Dr. Fu’s novel inhibitors block PME-1 activity in cells and in mice, resulting in increased activity of PME-1’s target, the major protein phosphatase, protein phosphatase 2A (PP2A). Previous research has suggested that PME-1 and PP2A may play a role in cancer growth and Alzheimer’s disease, but the lack of inhibitors for PME-1 hindered scientists’ ability to investigate these possibilities. The newly discovered inhibitors will help researchers decipher the contributions of PME-1 and PP2A to cancer and neurodegenerative disease. To donate your own chemicals, or to submit an assay for collaboration, see http://mli.nih.gov/mli/mlpcn/.

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