Profiling of drugs for membrane activity using liposomes as an in vitro model system

Drug Development and Industrial Pharmacy
L L GriniusAlan W Curnow

Abstract

The increasing size of chemical libraries being analyzed by high-throughput screening results in a growing number of active compounds that need to be assessed before moving forward in the drug development process. As a consequence, more rapid and highly sensitive strategies are required to accelerate the process of drug discovery without increasing the cost. Due to the fact that significant numbers of compounds from combinatorial libraries are hydrophobic in nature, approaches are needed to evaluate the potentialfor these compounds to interfere with the functions of biological membranes. The liposome system was used to detect agents that act as follows: (i) ionophores able to induce specific ion permeability, e.g., valinomycin for K+ and protonophoric uncouplers for H+; (ii) ion antiporters which exchange H+ for other ions, e.g., nigericin; (iii) agents that form low specificity ion channels in the membrane, e.g., gramicidin; and (iv) detergents and other membrane-disrupting agents. We propose using this liposome assay during the drug development process to identify compounds that have membrane activity and, as a consequence, produce a biological effect by altering the physico-chemical properties of the cell membrane rather tha...Continue Reading

References

Dec 4, 1975·The Journal of Membrane Biology·V S MarkinL S Jaguzhinsky
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Dec 10, 1968·Biochimica Et Biophysica Acta·H Schneider
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May 30, 1998·Analytical Biochemistry·S Clerc, Y Barenholz
Apr 21, 2001·The New England Journal of Medicine·C H Lawyer

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Citations

Jan 26, 2011·The Journal of Biological Chemistry·Wolfgang NörenbergMichael Schaefer
Aug 25, 2004·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Annika MälkiäKyösti Kontturi

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