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Molecular biology enabled us to understand the structure and function of genes and proteins. However, there are still many mysteries about protein–protein interaction, protein–small molecule interaction, post-transcriptional modification of protein and quality control of protein that are yet to be solved. If we have the specific inhibitor of the responsible protein, we can reveal the complex biological systems that have previously been considered difficult in molecular biology. RIKEN Natural Products Depository (NPDepo) is established to facilitate chemical biology research.

In this paper, the newly developed chemical array system for the screening of small molecule inhibitors is discussed. This method deserves a particular merit for the ligands (inhibitors) against non-enzymatic proteins. As a typical example, the screening against pirin will be shown. Pirin is a nuclear protein that exists in mammalian cells, but the function of it has not been well characterized. Therefore, we aimed to find a specific ligand of pirin and elucidated the function of pirin by using the small-molecule ligand as a bioprobe. We carried out the chemical array screening of human pirin fused with red fluorescent protein, and found a triphenyl compound (TphA) as a binding ligand. Through the intensive analyses of the effect of TphA, we found that pirin is involved in the melanoma cell migration.

It was known that pirin interacted with Bcl3 and enhanced the transcription activity of NF-kB. The increased Bcl3 expression was reported to enhance survival, proliferation and tumor malignancy in many tumor cell lines. However, TphA did not affect the cell viability but affected the migration of melanoma cells. Using TphA as the bioprobe for pirin, we revealed that the function of pirin is independent from NF-kB. Through this example, I would like to show the new possibility for searching new antitumor compounds.

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