RI-1 (chemical)

RI-1

Names
Preferred IUPAC name 3-Chloro-1-(3,4-dichlorophenyl)-4-(morpholin-4-yl)-1H-pyrrole-2,5-dione
Identifiers
CAS Number	415713-60-9
3D model (JSmol)	Interactive image
PubChem CID	1074953
UNII	S8WG8ZRQ99 Y
CompTox Dashboard (EPA)	DTXSID30360083
SMILES C1COCCN1C2=C(C(=O)N(C2=O)C3=CC(=C(C=C3)Cl)Cl)Cl
Properties
Chemical formula	C14H11Cl3N2O3
Molar mass	361.60 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

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.

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. PMC 3619390. 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.