RI-1

• CAT Number: I003506
• CAS Number: 415713-60-9
• Molecular Formula: C14H11Cl3N2O3
• Molecular Weight: 361.603
• Purity: ≥95%
• Synonyms: 3-chloro-1-(3,4-dichlorophenyl)-4-morpholin-4-ylpyrrole-2,5-dione
• Target: RAD51
• Solubility: DMSO 50 mg/mL; Water <1.1 mg/mL; Ethanol <1.1 mg/mL
• Storage: Store at -20°C
• IC50: 5-30 μM
• InChI: InChI=1S/C14H11Cl3N2O3/c15-9-2-1-8(7-10(9)16)19-13(20)11(17)12(14(19)21)18-3-5-22-6-4-18/h1-2,7H,3-6H2
• InChIKey: MWSUIZKGNWELRF-UHFFFAOYSA-N
• SMILES: C1COCCN1C2=C(C(=O)N(C2=O)C3=CC(=C(C=C3)Cl)Cl)Cl

RI-1(CAT: I003506) plays a pivotal role as a RAD51 inhibitor. RAD51 is a key protein involved in homologous recombination, a fundamental DNA repair process crucial for maintaining genomic stability. RI-1’s action as a RAD51 inhibitor suggests its potential in modulating DNA repair mechanisms. By interfering with RAD51 function, RI-1 may disrupt homologous recombination and impact the repair of DNA damage.

Reference

[1]. dke B, Logan HL, Kalin JH, Zelivianskaia AS, Cameron McGuire W, Miller LL, Stark JM, Kozikowski AP, Bishop DK, Connell PP. RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells. Nucleic Acids Res. 2012 May 9.
Abstract
Homologous recombination serves multiple roles in DNA repair that are essential for maintaining genomic stability. We here describe RI-1, a small molecule that inhibits the central recombination protein RAD51. RI-1 specifically reduces gene conversion in human cells while stimulating single strand annealing. RI-1 binds covalently to the surface of RAD51 protein at cysteine 319 that likely destabilizes an interface used by RAD51 monomers to oligomerize into filaments on DNA. Correspondingly, the molecule inhibits the formation of subnuclear RAD51 foci in cells following DNA damage, while leaving replication protein A focus formation unaffected. Finally, it potentiates the lethal effects of a DNA cross-linking drug in human cells. Given that this inhibitory activity is seen in multiple human tumor cell lines, RI-1 holds promise as an oncologic drug. Furthermore, RI-1 represents a unique tool to dissect the network of reaction pathways that contribute to DNA repair in cells.