CD47, also known as integrin-associated protein (IAP), is a cell membrane protein that belongs to the immunoglobulin superfamily and is highly expressed on the surface of tumor cell membranes. The molecular weight of CD47 is about 50 000. The N-terminus contains an IgV-like domain with 5 hydrophobic transmembrane regions; the C-terminus is a fragment containing 3-36 amino acids, located in the cytoplasmic region; the immunoglobulin domain glycosyl After lysing, it can bind to integrin, thrombospondin-1 (TSP-1) and SIRPα. By binding to integrins, CD47 mediates leukocyte adhesion and migration. CD47 interacts with TSP-1 to promote the development of various malignant tumors.  TSP-1 promotes the proliferation and survival of cutaneous T-cell lymphoma tumor cells, which can be inhibited by anti-CD47 neutralizing antibody or CD47 gene knockdown. In addition, CD47 binds to TSP-1, participates in the activation of platelets, inhibits NO-cGMP signaling in vascular epithelial cells, thereby causing vasoconstriction and vascular endothelial cell proliferation, and promoting cell proliferation. By binding to SIRPα, it inhibits macrophage phagocytosis, DC maturation and phagocytosis, antigen processing and presentation. Therefore, tumor therapy by targeting CD47 is a better drug development candidate. CD ComputaBio provides CD47 targeting services to customers to accelerate their research progress.

Figure 1. CD47 is the next checkpoint target for cancer immunotherapy. (Ridong Feng, et al.; 2020)

Our Services

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 technology (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

Our Advantage

• Our experts can quickly and accurately find atoms or groups that interact well with the active site of biological macromolecules through active site analysis software such as DRID, GREEN, HSITE, combined with Monte Carlo and simulated annealing techniques;
• We will flexibly select ligand-based (commonly used software such as Catalyst, Unity, etc.) or receptor-based (commonly used software such as DOCK, F1exX, GOLD, etc.) to search the database according to the characteristics of the target molecule;
• For cases where suitable lead compounds cannot be found in the compound database, we can design new compounds through software such as LUDI, Leapfrog, GROW, SPROU and LigBuilder.

Our Capabilities

CD ComputaBio has been working to combine computing power with the fields of chemistry and biology to simplify drug discovery, design, development and optimization.

Computer-aided or computer-simulated drug design can help accelerate and enable hit identification, hit rates, optimize ADME and toxicology profiles, and predict any safety issues. CD ComputaBio has accumulated deep expertise in discovery informatics, computational chemistry/molecular modeling, medicinal chemistry, structural biology, in vivo and in 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 drug development direction, and then select suitable drug candidates through low-cost, high-efficiency computer simulations to ensure high efficiency and low risk in the late-stage drug development process. Our computational biology team has extensive experience in CD47 target research. Please consult our professional team for details.

References

1. Jaiswal S, et al.; CD47is upregulated on circular hema-topoietic stem cells and leukemia cells to avoid Phagocytosis. Cell. 2009, 138:271-85.
2. Russ A, et al.; Blocking "don't eat me" signal of CD47-SIRPα in hematological malignancies, an in-depth review. Blood Rev. 2018, 32(6): 480-489.
3. Li CW, et al.; Activation of phagocytosis by immune checkpoint blockade. Front Med. 2018, 12(4): 473-480.
4. GuSL, et al.; CD47blockadeinhibitstumorprogression through promoting phagocytosis of tumor cells by M2 Polarized macrophages in endometrial cancer. J Immunol Res. 2018, 2018:6156757
5. Ridong Feng, et al.; CD47: the next checkpoint target for cancer immunotherapy. Critical Reviews in Oncology/Hematology. 2020, Volume 152, 103014.