Sprachman, Melissa M.Laughney, Ashley M.Kohler, Rainer H.Weissleder, Ralph2019-09-212014Sprachman, Melissa M., Ashley M. Laughney, Rainer H. Kohler, and Ralph Weissleder. 2014. “In Vivo Imaging of Multidrug Resistance Using a Third Generation MDR1 Inhibitor.” Bioconjugate Chemistry 25 (6): 1137–42. https://doi.org/10.1021/bc500154c.1043-18021520-4812http://nrs.harvard.edu/urn-3:HUL.InstRepos:41384274Cellular up-regulation of multidrug resistance protein 1 (MDR1) is a common cause for resistance to chemotherapy; development of third generation MDR1 inhibitors several of which contain a common 6,7-dimethoxy-2-phenethyl-1,2,3,4-tetrahydroisoquinoline substructure-is underway. Efficacy of these agents has been difficult to ascertain, partly due to a lack of pharmacokinetic reporters for quantifying inhibitor localization and transport dynamics. Some of the recent third generation inhibitors have a pendant heterocycle, for example, a chromone moiety, which we hypothesized could be converted to a fluorophore. Following synthesis and teasing of a small set of analogues, we identified one lead compound that can be used as a cellular imaging agent that exhibits structural similarity and behavior akin to the latest generation of MDR1 inhibitors.en-USJournal Article2019-09-2110.1021/bc500154c