BCRP is a semitransporter protein encoded by the ABCG2 gene, which is 72 kDa in size. It consists of six transmembrane domains whose homodimers or homotetramers are the active forms. BCRP localizes to the apical membrane of polarized cells, where it mediates unidirectional transport of substrates to the luminal side of the organ, thus acting as an efflux pump and playing a key role in maintaining the organ's barrier function. Studies have shown that BCRP protein is highly expressed in barrier tissues such as colon, small intestine, blood-brain barrier (BBB), placenta, and hepatic tubule membranes. Among these organs, BCRP first restricts the distribution of its substrates to organs such as the brain, testis, placenta, and the gastrointestinal tract (GIT). Second, it clears its substrates from excretory organs, mediates biliary and renal excretion, and sometimes directs intestinal secretion. BCRP is commonly co-expressed with MDR1 and shares many of its substrates, inhibitors, and inducers. BCRP is included in the list of important drug transporters that the FDA and EMA deem necessary to investigate NCE responsibility. BCRP is strongly induced in the lactating mammary gland and is also expressed at high levels on the apical surface of many tumor cell lines and transformed cell lines such as Caco-2. The study found, therefore, that BCRP is very marketable as a potential target for cancer therapy. CD ComputaBio provides BCRP targeting services to customers to accelerate their research progress.

Figure 1. A strategy for the development of a precision medicine approach based on histone acetylation in the ABCG2 gene in a mixed population. (Liming Chen, et al.; 2019)

Our Services

We provide professional services in computer-aided drug design.

In the early stages of drug development, guesswork in drug discovery can be expensive and time-consuming. Our team is here to jump it for you. With our services, your team will get:

• Significantly enhanced visualization of new binding sites for proteins developed for new drug development.
• Use professional computational physics-based algorithms to map proteins at an unprecedented level of detail.
• Well-designed small molecules optimized for affinity, specificity, and drug-like properties.
• Maximize atomic interactions between ligands and targets, using our specialized drug design platform to reveal where changes can be made to enhance drug-like properties without sacrificing affinity or specificity.
• Facilitate formulation of biologics through comprehensive excipient and protein-protein interaction profiling.

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

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 BCRP target research. Please consult our professional team for details.

References

1. Kage, K., et al.; Dominant-negative inhibition of breast cancer resistance protein as drug efflux pump through the inhibition of S-S dependent homodimerization. Int J Cancer. 2002. 97(5): p. 626-30.
2. Maliepaard, M., et al.; Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res. 2001. 61(8): p. 3458-64.
3. Jonker, J.W., et al.; The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk. Nat Med. 2005. 11(2): p. 127-9.
4. Liming Chen, et al.; Development of precision medicine approaches based on inter-individual variability of BCRP/ABCG2. Acta Pharmaceutica Sinica B. 2019, Volume 9, Issue 4, Pages 659-674.