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In vivo imaging of multidrug resistance using a third generation MDR1 inhibitor.

ABSTRACT: Cellular 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.

SUBMITTER: Sprachman MM

PROVIDER: S-EPMC4098115 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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In vivo imaging of multidrug resistance using a third generation MDR1 inhibitor.

Sprachman Melissa M MM Laughney Ashley M AM Kohler Rainer H RH Weissleder Ralph R

Bioconjugate chemistry 20140514 6

Cellular 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 hav ...[more]

PMID: 24806886

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