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Image-Guided Drug Design (Highlight in C&E News)

C&E News highlighted as a 'Science Concentrate' our work recently published in ACS Chemical Neuroscience. 

"To treat brain disorders such as schizophrenia, not only do drugs need to be potent, but they also need to slip past the defenses of the blood-brain barrier to reach their targets. Looking for ways to fill this tall order, a research team led by Jacob M. Hooker of Harvard Medical School and Sung Won Kim of NIH’s National Institute on Alcohol Abuse & Alcoholismhas developed a drug design strategy that combines brain imaging and lab assays (ACS Chem. Neurosci. 2014, DOI: 10.1021/cn500021p). The scientists began with a promising anticancer compound, MS-275, that blocks the enzyme histone deacetylase (HDAC). “It had been reported that it was a long-lasting inhibitor that gets into the brain,” Hooker tells C&EN. But when the team placed a radiolabel on the molecule and used positron emission tomography (PET) to image its uptake in the brains of baboons, they were disappointed. Undeterred, the researchers modified the compound, ran a few new versions of it through an assay to check for HDAC activity, and ran the PET scans again. After a few more rounds, the researchers hit upon a series of HDAC inhibitors capable of penetrating the brain. According to Hooker, the strategy offers a way “to optimize a series of candidates for brain penetration.” -Lauren K. Wolf