Lecture_8

Chemical messengers small proteins similar to

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- Chemical messengers - Small proteins similar to cytokines - Produced by macrophages during in±ammatory reaction - Attract T lymphocytes to site of infection
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31 Importance of chemokine co-receptor in HIV transmission
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32 The normal ligands for this receptor, RANTES , MIP-1 β , and MIP-1 α , are able to suppress HIV-1 infection in vitro . HIV uses the CCR5 co-receptor A number of new experimental HIV drugs, called entry inhibitors , have been designed to interfere with the interaction between CCR5 and HIV PRO140 ( Progenics ) = McAb, injected every other week Vicriviroc ( Schering Plough ) = noncompetitive allosteric antagonist of CCR5. Late stage clinical trials did not meet their primary efFcacy endpoints = not pursue regulatory approval Aplaviroc (GW-873140) ( GlaxoSmithKline ) = Development of Aplaviroc has been terminated due potential liver toxicity. Maraviroc (UK-427857) ( PFzer ) = full ±DA approval on August 6, 2007. Industry experts forecast annual Maraviroc sales of $500 million by 2011.
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Under selective pressure HIV will evolve to use another co-receptor Binding to alternative domains of CCR5, or • By binding to the receptor at a higher afFnity. Concerns surrounding CCR5 antagonists
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Chemical messengers Small proteins similar to cytokines...

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