Abstract
Chemokine receptors are a target of growing interest for new therapeutic drugs, as their role in multiple disease states has been demonstrated. The CXCR4/ CXCL12 pairing has been implicated in HIV and cancer, as well as chronic inflammatory diseases, including asthma and rheumatoid arthritis. HIV uses CXCR4 or CCR5 receptors in the key binding step of the infection process, leading to the idea that drugs could be developed to block this interaction. Cancer metastasis has also been linked to cellular communication via the chemokine pathways and hence, receptor antagonists could potentially inhibit this important pathway of disease progression. A wealth of data concerning small molecule CXCR4 receptor antagonists has been generated over the last few years, as a variety of these small molecules have been tested, and the understanding of structure activity relationships has improved. Here, we review the developing area of small molecule CXCR4 antagonists and the rapidly increasing amount of data from biological studies. Both peptidic and non-peptidic compounds have been investigated. In particular, we focus on AMD3100 and bismacrocyclic analogues, the most extensively studied class of CXCR4 antagonists, and the recent developments in this area.
Keywords: CXCR4, CXCL12, chemokine receptors, AMD3100, HIV, cancer, macrocycle, metal complexes
Current Medicinal Chemistry
Title: Small Molecule CXCR4 Chemokine Receptor Antagonists: Developing Drug Candidates
Volume: 14 Issue: 21
Author(s): Abid Khan, John Greenman and Stephen J. Archibald
Affiliation:
Keywords: CXCR4, CXCL12, chemokine receptors, AMD3100, HIV, cancer, macrocycle, metal complexes
Abstract: Chemokine receptors are a target of growing interest for new therapeutic drugs, as their role in multiple disease states has been demonstrated. The CXCR4/ CXCL12 pairing has been implicated in HIV and cancer, as well as chronic inflammatory diseases, including asthma and rheumatoid arthritis. HIV uses CXCR4 or CCR5 receptors in the key binding step of the infection process, leading to the idea that drugs could be developed to block this interaction. Cancer metastasis has also been linked to cellular communication via the chemokine pathways and hence, receptor antagonists could potentially inhibit this important pathway of disease progression. A wealth of data concerning small molecule CXCR4 receptor antagonists has been generated over the last few years, as a variety of these small molecules have been tested, and the understanding of structure activity relationships has improved. Here, we review the developing area of small molecule CXCR4 antagonists and the rapidly increasing amount of data from biological studies. Both peptidic and non-peptidic compounds have been investigated. In particular, we focus on AMD3100 and bismacrocyclic analogues, the most extensively studied class of CXCR4 antagonists, and the recent developments in this area.
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Cite this article as:
Khan Abid, Greenman John and Archibald J. Stephen, Small Molecule CXCR4 Chemokine Receptor Antagonists: Developing Drug Candidates, Current Medicinal Chemistry 2007; 14 (21) . https://dx.doi.org/10.2174/092986707781696618
DOI https://dx.doi.org/10.2174/092986707781696618 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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