RI-1 (chemical) explained

RI-1 is a selective inhibitor of RAD51, which is a central gene molecule of homologous recombination, with IC₅₀ ranging from 5 to 30 μM.^[1]

Antitumor mechanism

RAD51 is a eukaryote gene, encoding RAD51 protein that participates in DNA damage induction and complex signal pathway of cell cycle checkpoint of homologous recombination in cells. However, over-expression of RAD51 may lead the occurrence and development progress of tumours and besides, the insensitivity of tumours to chemoradiotherapy. At present, over-expression of RAD51 has been found in many kinds of human cancers, such as breast cancer, lung cancer and ovarian cancer.

RI-1 inhibits the over-expression of RAD51 in cancer cells by bonding covalently to the surface of RAD51 protein at Cys 319 and irreversibly loosen a protein-protein interface that is essential for filament formation and recombinase activity.

Targeted drugs to RAD51 has the prospect to be a new generation of oncologic drugs, like RI-1. It is also a unique tool for mechanism studies of DNA repair.^[2]

Literature

• Budke . B. . etal . 2013 . An optimized RAD51 inhibitor that disrupts homologous recombination without requiring Michael acceptor reactivity. . J Med Chem . 56 . 1. 254–63 . 10.1021/jm301565b . 23231413 . 3619390.
• Budke . B. . etal . 2012 . RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells. . Nucleic Acids Res . 40 . 15. 7347–57 . 10.1093/nar/gks353 . 22573178. 3424541 .

Notes and References

1. Web site: Biological activity of RI-1 in vitro. selleck chemicals .
2. Budke B, etal . Aug 2012. 10.1093/nar/gks353 . 40 . 15. 7347–57. Nucleic Acids Res.. RI-1:a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells.. 22573178. 3424541.