Anticancer Research

Cancer is a main cause of death worldwide. It had been reported that nearly 10 million deaths in 2020 and almost 20 million new cancer cases are diagnosed each year. Preventing cancer becomes more important and new drug development is also becoming more urgent. Cryogenic electron microscopy (cryo-EM), as an emerging method for structural biology, has been attracted much attention in anticancer research. Most anticancer drug targets are the DNA, RNA, or proteins, which are present only in cancer cells. By analyzing the macromolecular complexes between receptors and antibodies or small molecule drugs, the interaction mechanism can be explored, which improves the understanding of the interaction mode between drugs and their targets, thus accelerating the process of drug design.

Figure 1. The general strategy for targeted therapies (Sung H, et al. 2021)

Cryo-EM method has solved lots of drug target structures and helped with structure-based functional research. For instance, the structure of the human ACLY tetramer complex was solved with NDI-091143 and ADP by cryo-EM. This study improved the understanding of tumor metastasis and diffusion and laid a solid foundation for drug development to treat cancer and metabolic disorders.

Figure 2. The overall structure of the human ACLY tetramer in complex with NDI-091143 and ADP (A), Overlay of the structures of the citrate domain in complex with NDI-091143 and the domain in complex with citrate (B) (Sung H, et al. 2021)

With the hardware and algorithm revolution, cryo-EM can generate atomic-resolution structures for macromolecules and visualize the binding of therapies drugs (such as small-molecule ligands, peptide, RNA, and DNA) in the macromolecules. It provides unprecedented insights into the molecular mechanism. With our cryo-EM platform, Creative Biostructure can provide a variety of structural analysis services to help our customers in anticancer research.

If you are interested in our services, please feel free to contact us. We are looking forward to cooperating with you.

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References

1. Sung H, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021. 71(3): 209-249.
2. Unoki M, Kumamoto K. ING proteins as potential anticancer drug targets. Current Drug Targets. 2009, 10(5): 442-454.