Inhibition of HIV infection by bicyclams, highly potent and specific CXCR4 antagonists.

E De Clercq

Journal: Molecular pharmacology 2000;57(5):833-9

PMID: 10779364

Abstract

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.

Address: Rega Institute for Medical Research, Department of Microbiology and Immunology, Katholieke Universiteit, Leuven, Belgium. [email protected]

Link outs

Free resources

Medical:

https://medlineplus.gov/hivmedicines.html

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Miscellaneous:

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MeSH Terms: Amino Acid Sequence, Anti-HIV Agents, Benzylamines, Chemokines, CXC, Cyclams, HIV Infections, HIV-1, Heterocyclic Compounds, Humans, Molecular Sequence Data, Receptors, CXCR4, Structure-Activity Relationship