Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase that plays a key role in regulating fundamental cellular processes such as morphogenesis, differentiation, proliferation, adhesion, migration, invasion, and matrix remodeling. Therefore, dysregulation of DDR1 can be attributed to a variety of human diseases, such as non-small cell lung cancer (NSCLC), ovarian cancer, glioblastoma, breast cancer, Alport syndrome, spondyloepiphyseal dysplasia, short-limbed hand, and some inflammatory diseases and neurodegenerative diseases. The protein encoded by this gene is an RTK that is widely expressed in normal and transformed epithelial cells and activated by various types of collagen. DDR1 proteins have regions of homology to colistin discoids in their extracellular domain I. Its related pathways include ERK signaling and activation of camp-dependent PKA. Since the target identification in the early 1990s, people have been working on the development of DDR inhibitors, and DDR inhibitors already exist for clinical treatment. This shows that DDR1 as a drug target is an option to meet clinical and market needs and has great potential. CD ComputaBio provides DDR1 targeting services to customers to accelerate the progress of their research.

Our Services

• Targeted Protein Structural Analysis

The crystal structure of DDR1 protein molecule can be obtained by X-ray single crystal diffraction technology or 3D structure simulation of existing homologous molecules, and then the information of its binding site can be determined;

• Analysis of target protein properties

We can use molecular simulation software to analyze the structural properties of the DDR1 binding site, such as electrostatic field, hydrophobic field, and distribution of hydrogen bonding sites;

• Lead Candidate Search

After obtaining the binding site information, use database search software or new drug molecular design technology to screen molecules whose molecular morphology and physicochemical properties match the DDR1 action site;

• Candidate compound validation

Finally, we synthesize and test the screened molecules, and after multiple rounds of screening, suitable lead compounds can be found.

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;
• Flexible selection of ligand-based (commonly used software such as Catalyst and Unity, etc.) and receptor-based (commonly used software such as DOCK, F1exX and GOLD, etc.) search methods for database search;
• In the event that a suitable lead compound cannot be found in the compound database, we offer a new compound synthesis service, which enables new compound design through advanced bioinformatics software.

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 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 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 DDR1 targets. Please consult our professional team for details.

References

1. Valencia K, et al.; Inhibition of collagen receptor discoidin domain receptor-1 (DDR1) reduces cell survival, homing, and colonization in lung cancer bone metastasis. Clin Cancer Res. 2012 Feb 15;18(4):969-80.
2. Dorison A, et al.; The Role of Discoidin Domain Receptor 1 in Inflammation, Fibrosis and Renal Disease. Nephron. 2017;137(3):212-220.
3. Jing H, et al.; Discoidin domain receptor 1: New star in cancer-targeted therapy and its complex role in breast carcinoma. Oncol Lett. 2018,15(3):3403-3408.
4. Ahmed Elkamhawy, et al.; The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer. Int. J. Mol. Sci. 2021, 22(12), 6535.