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Visualizing Ligand Binding to a GPCR In Vivo Using NanoBRET.

ABSTRACT: The therapeutic action of a drug depends on its ability to engage with its molecular target in vivo. However, current drug discovery strategies quantify drug levels within organs rather than determining the binding of drugs directly to their specific molecular targets in vivo. This is a particular problem for assessing the therapeutic potential of drugs that target malignant tumors where access and binding may be impaired by disrupted vasculature and local hypoxia. Here we have used triple-negative human breast cancer cells expressing ?₂-adrenoceptors tagged with the bioluminescence protein NanoLuc to provide a bioluminescence resonance energy transfer approach to directly quantify ligand binding to a G protein-coupled receptor in vivo using a mouse model of breast cancer.

SUBMITTER: Alcobia DC

PROVIDER: S-EPMC6137713 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Visualizing Ligand Binding to a GPCR In Vivo Using NanoBRET.

Alcobia Diana C DC Ziegler Alexandra I AI Kondrashov Alexander A Comeo Eleonora E Mistry Sarah S Kellam Barrie B Chang Aeson A Woolard Jeanette J Hill Stephen J SJ Sloan Erica K EK

iScience 20180811

The therapeutic action of a drug depends on its ability to engage with its molecular target in vivo. However, current drug discovery strategies quantify drug levels within organs rather than determining the binding of drugs directly to their specific molecular targets in vivo. This is a particular problem for assessing the therapeutic potential of drugs that target malignant tumors where access and binding may be impaired by disrupted vasculature and local hypoxia. Here we have used triple-negat ...[more]

PMID: 30240618

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