Trisha Shetty (Editor)

RI 1(RAD51 inhibitor II)

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Formula
  
C14H11Cl3N2O3

RI-1(RAD51 inhibitor II)

IUPAC ID
  
3-Chloro-1-(3,4-dichlorophenyl)-4-(4-morpholinyl)-1H-pyrrole-2,5-dione

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.

Contents

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.

Literature

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

    • References

    RI-1(RAD51 inhibitor II) Wikipedia
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