Citations
1 publicationsPublications from researchers using this productDescription
RI-1 is a RAD51 protein inhibitor, with IC50 values ranging from 5 to 30μM[1]. RI-1 contains a chloromaleimide group that functions chemically as a Michael acceptor, thereby inhibiting RAD51 by covalently binding to the Cys319 residue, and RI-1 disrupts RAD51-ssDNA binding by preventing oligomerization of RAD51 into filaments on DNA[2]. RI-1 has been widely used to increase the sensitivity of glioblastoma stem cell-like cells to ionizing radiation and to interfere with the DNA repair process[3].
In vitro, RI-1 treatment (20µM) in combination with etoposide (1µM) for 48 hours significantly inhibited the viability of FLO-1 cells and induced cell apoptosis[4]. Treatment with 20µM RI-1 for 48 hours markedly reduced the camptothecin-induced genomic instability of MCF7, HCT116, and OE19 cells[5]. Treatment with 1.5µM RI-1 for 3 weeks following 2Gy irradiation (2h) significantly reduced the survival of glioblastoma cells and decreased the expression level of SOX2 mRNA[6].
In vivo, RI-1 treatment via intraperitoneal injection at a dose of 5mg/kg every other day for 36 days significantly inhibited the growth of HeLa xenograft tumors in mice[7]. Intraperitoneal injection of RI-1 at a dose of 50mg/kg every 3 days for 30 days significantly reduced tumor growth in the MDA-MB-157 xenograft mouse model without affecting body weight[8].
References:
[1] Budke B, Logan H L, Kalin J H, et al. RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells[J]. Nucleic acids research, 2012, 40(15): 7347-7357.
[2] Budke, Brian, et al. "Recent developments using small molecules to target RAD51: how to best modulate RAD51 for anticancer therapy?." ChemMedChem 11.22 (2016): 2468-2473.
[3] Balbous, Anaïs, et al. "A radiosensitizing effect of RAD51 inhibition in glioblastoma stem-like cells." BMC cancer 16.1 (2016): 604.
[4] Liao C, Zhao J, Kumar S, et al. RAD51 inhibitor reverses etoposide-induced genomic toxicity and instability in esophageal adenocarcinoma cells[J]. Archives of clinical toxicology, 2020, 2(1): 3.
[5] Liao C, Talluri S, Zhao J, et al. RAD51 is implicated in DNA damage, chemoresistance and immune dysregulation in solid tumors[J]. Cancers, 2022, 14(22): 5697.
[6] King H O, Brend T, Payne H L, et al. RAD51 is a selective DNA repair target to radiosensitize glioma stem cells[J]. Stem cell reports, 2017, 8(1): 125-139.
[7] Chen Q, Cai D, Li M, et al. The homologous recombination protein RAD51 is a promising therapeutic target for cervical carcinoma[J]. Oncology reports, 2017, 38(2): 767-774.
[8] Shi Y, Jin J, Wang X, et al. DAXX, as a tumor suppressor, impacts DNA damage repair and sensitizes BRCA-proficient TNBC cells to PARP inhibitors[J]. Neoplasia, 2019, 21(6): 533-544.
Protocol
| Cell experiment [1]: | |
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Cell lines |
FLO-1 cells |
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Preparation Method |
FLO-1 cells were cultured in DMEM medium supplemented with 10% fetal bovine serum (FBS), 2mM glutamine, and 1% penicillin-streptomycin at 37°C in 5% CO2/atmosphere. FLO-1 cells were seeded onto 96-well microplates (1×104 cells/well) and cultured for 24h. The cells were treated with PBS or RI-1 at different concentrations (0, 1, 10, and 20µM) in the presence of 1µM etoposide. After 48h incubation, cell viability was assessed. |
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Reaction Conditions |
0, 1, 10, and 20µM; 48h |
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Applications |
RI-1 treatment reduced the cell viability of FLO-1 cells in a dose-dependent manner in the presence of etoposide. |
| Animal experiment [2]: | |
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Animal models |
Female BALB/c-nude mice |
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Preparation Method |
Female BALB/c-nude mice (6-weeks old) were housed under controlled temperature (21-23°C), humidity (30-35%) and light cycle (7:00 AM to 7:00 PM) and maintained on a standard rodent diet. HeLa Cells (1×107) in the exponential growth phase were collected and suspended in 200µl phosphate-buffered saline and then injected subcutaneously into the posterior side of mice. RI-1 (5mg/kg in 200µl phosphate-buffered saline) was injected intraperitoneally every other day for 36 days into mice when the tumor volume reached 120mm3. Analyze the tumor volume of the mice every 3 days. |
|
Dosage form |
5mg/kg; every other day; 36 days; i.p. |
|
Applications |
RI-1 treatment significantly inhibited tumor growth in mice with HeLa xenografts. |
References: [1] Liao C, Zhao J, Kumar S, et al. RAD51 inhibitor reverses etoposide-induced genomic toxicity and instability in esophageal adenocarcinoma cells[J]. Archives of clinical toxicology, 2020, 2(1): 3. [2] Chen Q, Cai D, Li M, et al. The homologous recombination protein RAD51 is a promising therapeutic target for cervical carcinoma[J]. Oncology reports, 2017, 38(2): 767-774. | |
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