Chemokines are a superfamily of chemokines with similar molecular structures. According to the difference in the arrangement and distribution of the first two cysteine residues in the N-terminal highly conserved sequence in their primary structure, the It is divided into 4 categories: C, CC, CXC and CX3C. Chemokine receptors are 7-transmembrane G protein-coupled receptor (GPCR) proteins. According to the different types of binding chemokines, it is divided into CXC receptors and CC receptors. Chemokines bind to the extracellular N-terminus of chemokines, mediate the intracellular serine/threonine phosphorylation of receptor proteins, and activate the gene transcription of cell motility, invasion, extracellular matrix interaction, and cell survival through different transmembrane signal transduction pathways.
Figure 1. CCR5 and its ligands. (Michael M Lederman, et al.; 2007)
CCR5 is a receptor for beta chemokine and has functions in regulating the migration, proliferation and immunity of T cells and monocyte/macrophage cell lines. The receptor for this chemokine is mainly expressed on the cell membranes of quiescent memory T lymphocytes, monocytes and immature dendritic cells, etc. It is also important coreceptor when human immunodeficiency virus type 1 (HIV-1) invades the human body. However, the biological function of CCR5 is not limited to mediating the chemotaxis of immune cells and its role as a co-receptor for HIV invading CD4 + T cells, but also participates in the occurrence and development of tumors. Existing studies have shown that CCR5 not only affects the occurrence and development of tumors through inflammatory responses, but also regulates the occurrence, proliferation and metastasis of tumors by interacting with tumor-related genes. For example, the CCL5-CCR5 axis affects the process of immune cell infiltration. Therefore, tumor therapy by targeting CCR5 is a better drug development direction. CD ComputaBio provides CCR5 targeting services to customers to accelerate their research progress.
Our Services
We provide professional services in computer-aided drug design.
Binding site recognition
- Binding pocket searches using known ligands
- Binding pocket recognition by pharmacophore generation
- Binding pocket identification by fragment screening
Database Filtering
Receptor-based 3D pharmacophore models
Ligand formation using existing technologies (catalysts, etc.)
Ligand ranking
Ligand Optimization
- Qualitative ligand optimization via FragMaps visualization
- Quantitative assessment of the contribution of ligand atoms to binding
- Quantitative estimation of relative ligand affinity
- Quantitative estimation of chemical transformations of bulk ligands
Fragment-Based Ligand Design
- Identification of fragment binding sites
- Estimation of ligand affinity after fragment ligation
- Expansion of fragment types
Why work with us?
- Industry-standard software and hardware
- Proprietary design concepts and tools
- Highly experienced scientists
- Strong track record of success
- Tight integration with allied disciplines
Our Capabilities
In each therapeutic area, CD ComputaBio has accumulated deep expertise in discovery informatics, computational chemistry/molecular modeling, medicinal chemistry, structural biology, in vivo andin vitro pharmacology, and translational science. During the drug discovery process, our team focuses on early lead compounds in different target classes and uses a wide range of techniques, including molecular screening, molecular modeling, medicinal chemistry, structural biology, bioinformatics and computational chemistry, to identify new target the direction of drug development, and then select suitable drug candidates through low-cost, high-efficiency computer simulations to ensure high efficiency and low risk in the later drug development process. Our computational biology team has extensive experience in the research of CCR5 targets. Please consult our professional team for details.
References
- Kakinuma T, et al.; Chemokines, chemokine receptors, and cancer metastasis. J Leukoc Biol. 2006, 79(4): 639-651.
- Slettenaar VIF, et al.; The chemokine network: a target in cancer biology? Adv Drug Deliv Rev. 2006, 58 (8): 962-974.
- Feng Y, et al.; HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G proteincoupled receptor. Science. 1996, 272(5263): 872-877.
- Kuipers HF, et al.; CC chemokine receptor 5 gene promoter activation by the cyclic AMP response element binding transcription factor. Blood. 2008, 112(5): 1610-1619.
- Michael M Lederman, et al.; CCR5 and its ligands: a new axis of evil? Nature Immunology. 2007, volume 8, pages1283–1285
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