Inhibition of HIV infection by bicyclams, highly potent and specific CXCR4 antagonists.
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.
De Clercq
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Rega Institute for Medical Research, Department of Microbiology and Immunology, Katholieke Universiteit, Leuven, Belgium. erik.declercq@rega.kuleuven.ac.be
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001596:Benzylamines; D019743:Chemokines, CXC / Q000378:metabolism; D000080027:Cyclams; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control; D015497:HIV-1 / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008969:Molecular Sequence Data; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D001596:Benzylamines; D019743:Chemokines, CXC; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor