Theranostics 2013; 3(1):47-75. doi:10.7150/thno.5376


Small Molecule Inhibitors of CXCR4

Bikash Debnath1, Shili Xu1, Fedora Grande2, Antonio Garofalo2, Nouri Neamati1✉

1. Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC 304, Los Angeles, CA 90089-9121, USA.
2. Dipartimento di Scienze Farmaceutiche, Università della Calabria, 87036 Arcavacata di Rende, CS Italy.

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Debnath B, Xu S, Grande F, Garofalo A, Neamati N. Small Molecule Inhibitors of CXCR4. Theranostics 2013; 3(1):47-75. doi:10.7150/thno.5376. Available from

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CXCR4 is a G-protein-coupled receptor involved in a number of physiological processes in the hematopoietic and immune systems. The SDF-1/CXCR4 axis is significantly associated with several diseases, such as HIV, cancer, WHIM syndrome, rheumatoid arthritis, pulmonary fibrosis and lupus. For example, CXCR4 is one of the major co-receptors for HIV entry into target cells, while in cancer it plays an important role in tumor cell metastasis. Several promising CXCR4 antagonists have been developed to block SDF-1/CXCR4 interactions that are currently under different stages of development. The first in class CXCR4 antagonist, plerixafor, was approved by the FDA in 2008 for the mobilization of hematopoietic stem cells and several other drugs are currently in clinical trials for cancer, HIV, and WHIM syndrome. While the long-term safety data for the first generation CXCR4 antagonists are not yet available, several new compounds are under preclinical development in an attempt to provide safer and more efficient treatment options for HIV and cancer patients.

Keywords: CXCR4, antagonists, HIV, cancer, rheumatoid arthritis, WHIM syndrome, lupus.