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ABC Transporters: Importer01:27

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ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
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ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
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Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
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Karanjin interferes with ABCB1, ABCC1, and ABCG2.

Martin Michaelis, Florian Rothweiler, Thomas Nerreter

    Journal of Pharmacy & Pharmaceutical Sciences : a Publication of the Canadian Society for Pharmaceutical Sciences, Societe Canadienne Des Sciences Pharmaceutiques
    |April 17, 2014
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    Summary

    The furanoflavonol karanjin significantly impacts ATP-binding cassette (ABC) transporters, affecting drug transport and potentially altering drug pharmacokinetics. Karanjin shows stronger effects on ABCB1, ABCC1, and ABCG2 than other flavonoids.

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    Area of Science:

    • Pharmacology
    • Biochemistry
    • Drug Discovery

    Background:

    • ATP-binding cassette (ABC) transporters, including ABCB1, ABCC1, and ABCG2, are crucial for drug absorption, distribution, elimination, and multidrug resistance in cancer.
    • Flavonoids are known modulators of ABC transporter activity.
    • Karanjin is a furanoflavonol with potential therapeutic applications.

    Purpose of the Study:

    • To investigate the effect of karanjin on ABCB1, ABCC1, and ABCG2-mediated drug transport.
    • To compare karanjin's effects with those of apigenin, genistein, and naringenin.
    • To determine karanjin's impact on ABC transporter ATPase activity.

    Main Methods:

    • Utilized cell lines expressing specific ABC transporters (ABCB1, ABCC1, ABCG2).
    • Employed fluorescent and cytotoxic substrates and inhibitors to assess transporter function.
    • Measured the effects of flavonoids on ABC transporter ATPase activity.

    Main Results:

    • Karanjin inhibited drug efflux mediated by ABCB1, ABCC1, and ABCG2.
    • Karanjin enhanced the ATPase activity of all three investigated ABC transporters.
    • Karanjin demonstrated more potent effects than control flavonoids, notably inhibiting ABCB1 at low concentrations (~1 µM).

    Conclusions:

    • Karanjin's interaction with ABCB1, ABCC1, and ABCG2 warrants consideration for its therapeutic development.
    • The observed effects on ABC transporters may influence the pharmacokinetics of co-administered drugs.