Chemistry:RI-1 (chemical)
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| Preferred IUPAC name
3-Chloro-1-(3,4-dichlorophenyl)-4-(morpholin-4-yl)-1H-pyrrole-2,5-dione | |
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3D model (JSmol)
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PubChem CID
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| Properties | |
| 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.[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]
References
- ↑ "Biological activity of RI-1 in vitro". selleck chemicals. http://www.selleckchem.com/products/ri-1.html.
- ↑ "RI-1:a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells.". Nucleic Acids Res. 40 (15): 7347–57. Aug 2012. doi:10.1093/nar/gks353. PMID 22573178.
Literature
- Budke, B. (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. (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. PMID 22573178.
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