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Nat Rev Drug Discov. 2011 Dec 16;11(1):25-36. doi: 10.1038/nrd3404.

Interfacial inhibitors: targeting macromolecular complexes.

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Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA.

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  • Nat Rev Drug Discov. 2012 Mar;11(3):250.


Interfacial inhibitors belong to a broad class of natural products and synthetic drugs that are commonly used to treat cancers as well as bacterial and HIV infections. They bind selectively to interfaces as macromolecular machines assemble and are set in motion. The bound drugs transiently arrest the targeted molecular machines, which can initiate allosteric effects, or desynchronize macromolecular machines that normally function in concert. Here, we review five archetypical examples of interfacial inhibitors: the camptothecins, etoposide, the quinolone antibiotics, the vinca alkaloids and the novel anti-HIV inhibitor raltegravir. We discuss the common and diverging elements between interfacial and allosteric inhibitors and give a perspective for the rationale and methods used to discover novel interfacial inhibitors.

[Indexed for MEDLINE]

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