MDR-1 is widely distributed throughout the human body. It is specifically expressed in the intestinal epithelium, where it pumps xenobiotics (such as toxins or drugs) that may be inadvertently ingested into the ileal lumen, in hepatocytes through the bile ducts to pump them into bile, and in hepatocytes near the kidneys The distal tubule pumps them into the urine (in the proximal tubule) and back into the capillaries in the capillary endothelial cells that make up the blood-brain barrier and blood-testis barrier, protecting sensitive organs from damage. The normal excretion of xenobiotics from the ileal lumen by MDR-1 reduces the efficacy of some oral drugs that have been found to be MDR-1 substrates. In addition, some cancer cells also overexpress large amounts of MDR-1, making these cancer cells multidrug-resistant. Therefore, in order to achieve the purpose of curing cancer, targeting MDR-1 as a drug is an excellent choice. CD ComputaBio provides MDR-1 targeting services to customers to accelerate their research progress.

Figure1. Schematic model in regulations of MDR1 and P-glycoprotein. (Kazuhiro Katayama, et al.; 2014)

Our Services

• Targeted Protein Structural Analysis

Using X-ray single crystal diffraction technology and the 3D structure of the known homologous molecule to simulate the structure of the MDR-1 molecule, and then infer its binding site;  

• Analysis of Target Protein Properties

Our experienced professional researchers use state-of-the-art molecular simulation software to analyze the structural properties of the MDR-1 binding site, such as electrostatic field, hydrophobic field, hydrogen bonding site distribution, etc.;

• Lead Candidate Search

Use database search software or new drug molecular design technology to screen lead compounds whose molecular morphology and physicochemical properties match the action site of MDR-1;  

• Candidate Compound Validation

These molecules are synthesized and tested for biological activity, and after several screening cycles, 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;
• 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

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 MDR-1 targets. Please consult our professional team for details.

References

1. Kazuhiro Katayama, et al.; Regulation of P-glycoprotein/ABCB1/MDR1 in human cancer cells. New Journal of Science. 2014, 2014(2):1-10
2. Mealey KL. Therapeutic implications of the MDR-1 gene. J Vet Pharmacol Ther. 2004, 27(5):257-64.
3. N Montazami, et al.; New insights into the mechanisms of multidrug resistance in cancers. Cellular and molecular biology (Noisy-le-Grand, France). 2015, 61(7):70-80.