Abstract:
:The two G protein-coupled receptors (GPCRs) C-X-C chemokine receptor type 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are part of the class A chemokine GPCR family and represent important drug targets for human immunodeficiency virus (HIV) infection, cancer, and inflammation diseases. CXCR4 is one of only three chemokine receptors with a US Food and Drug Administration approved therapeutic agent, the small-molecule modulator AMD3100. In this review, known modulators of the two receptors are discussed in detail. Initially, the structural relationship between receptors and ligands is reviewed on the basis of common structural motifs and available crystal structures. To date, no atypical chemokine receptor has been crystallized, which makes ligand design and predictions for these receptors more difficult. Next, the selectivity, receptor activation, and the resulting ligand-induced signaling output of chemokines and other peptide ligands are reviewed. Binding of pepducins, a class of lipid-peptides whose basis is the internal loop of a GPCR, to CXCR4 is also discussed. Finally, small-molecule modulators of CXCR4 and ACKR3 are reviewed. These modulators have led to the development of radio- and fluorescently labeled tool compounds, enabling the visualization of ligand binding and receptor characterization both in vitro and in vivo. SIGNIFICANCE STATEMENT: To investigate the pharmacological modulation of CXCR4 and ACKR3, significant effort has been focused on the discovery and development of a range of ligands, including small-molecule modulators, pepducins, and synthetic peptides. Imaging tools, such as fluorescent probes, also play a pivotal role in the field of drug discovery. This review aims to provide an overview of the aforementioned modulators that facilitate the study of CXCR4 and ACKR3 receptors.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Adlere I,Caspar B,Arimont M,Dekkers S,Visser K,Stuijt J,de Graaf C,Stocks M,Kellam B,Briddon S,Wijtmans M,de Esch I,Hill S,Leurs Rdoi
10.1124/mol.119.117663subject
Has Abstractpub_date
2019-12-01 00:00:00pages
737-752issue
6eissn
0026-895Xissn
1521-0111pii
mol.119.117663journal_volume
96pub_type
杂志文章,评审abstract::The role of the cGMP-dependent protein kinase (cGK) and one of its major substrates, the vasodilator-stimulated phosphoprotein (VASP), in the regulation of a receptor-evoked calcium response was investigated. The human type I beta cGK was stably transfected in human embryonic kidney 293 cells and Swiss mouse 3T6 fibro...
journal_title:Molecular pharmacology
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abstract::The effect of lysosomotropic agents and secretory inhibitors were compared with verapamil for their effect on the activity of doxorubicin (DOX) in multiple drug-resistant (MDR) P388 leukemia cells (P388R) and in blocking anthracycline efflux from these cells. Agents known to interact with the plasma membrane did not p...
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abstract::Healing of gastrointestinal mucosal lesions occurs through two processes: an early one involving cell migration and a later one in which cell division replaces lost cells. Both processes require the presence of polyamines, but the mechanism of action of these compounds is unknown. In the present study, we examined the...
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journal_title:Molecular pharmacology
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doi:10.1124/mol.108.052209
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
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更新日期:2010-06-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-07-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
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doi:10.1124/mol.64.6.1402
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-06-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 评论,杂志文章,评审
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journal_title:Molecular pharmacology
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doi:
更新日期:1992-04-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00