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Vol. 57, Issue 5, 833-839, May 2000
Rega Institute for Medical Research, Department of Microbiology and
Immunology, Division of Virology and Chemotherapy, Katholieke
Universiteit, Leuven, Leuven, Belgium
The bicyclams represent a new entity of low-molecular weight molecules
that inhibit human immunodeficiency virus (HIV) infection through a
specific blockade of CXCR4 (fusin), the receptor for the CXC chemokine
SDF-1 (soluble-derived factor), which is also used as coreceptor
by T-lymphotropic HIV strains to enter their target cells. The bicyclam
AMD3100 or
1,1'-[1,4-phenylenebis(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane octahydrochloride dihydrate, is able to block the CXCR4 receptor and to
inhibit HIV replication at nanomolar concentrations while not being
toxic to the host cells at 100,000-fold higher concentrations. It is
the most specific and most potent CXCR4 antagonist that has been
described to date.
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