Targeting CXCR4 in HIV cell-entry inhibition
A Steen1, T W Schwartz, M M Rosenkilde
1Department of Neuroscience and Pharmacology, Faculty of Health Sciences, Copenhagen University, Copenhagen, Denmark.
Mini Reviews in Medicinal Chemistry
|January 22, 2010
Summary
This review covers the development of CXCR4 antagonists for HIV treatment, from chemokines to small molecules like AMD070, aiming to prevent coreceptor switching and delay AIDS progression.
Area of Science:
- Virology
- Immunology
- Medicinal Chemistry
Background:
- HIV-1 entry relies on coreceptors CXCR4 and CCR5.
- Approximately 50% of HIV infections involve a switch from CCR5 (R5) to CXCR4 (X4) strains.
- CXCR4 antagonists can delay AIDS by preventing this coreceptor switch.
Purpose of the Study:
- To review drug discovery efforts targeting CXCR4 for anti-HIV therapies.
- To explore the evolution of CXCR4 antagonists from chemokines to small molecules.
Main Methods:
- Review of scientific literature on CXCR4 antagonists.
- Analysis of drug development pathways for HIV-1 entry inhibitors.
Main Results:
- Chemokines and modified versions show inhibitory potential but have drawbacks.
- Small-molecule antagonists like AMD3100 target CXCR4 but lack oral bioavailability.
- Orally active non-peptide antagonists, such as AMD070, have been developed and are in clinical trials.
Conclusions:
- The development of orally active small-molecule CXCR4 antagonists represents a significant advancement in anti-HIV treatment.
- Targeting CXCR4 offers a promising strategy to combat HIV-1 infection by inhibiting viral entry.
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