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RI-1
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
RI-1图片
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
5mg电议
10mg电议
50mg电议

产品介绍
RI-1 是一种 RAD51 抑制剂,IC50 范围为 5 至 30 μM。 RI-1 在半胱氨酸 319 处与 RAD51 蛋白表面共价结合。RI-1 通过直接结合作为 RAD51 细丝中蛋白质亚基之间界面的蛋白质表面使 RAD51 失活。 RI-1 可以破坏人类细胞中的同源重组。

Cell lines

HeLa, MCF-7,U2OS cells

Preparation Method

Human cell lines were sequentially incubated for 24 h in media containing varying concentrations of mitomycin C, followed by 24 h in media containing RI-1. Cells were then allowed to grow in drug-free media for an additional 7–9 days.

Reaction Conditions

24h,15 μM, 25 μM

Applications

In all three cell types, RI-1 significantly sensitized cells to MMC. The magnitude of sensitization was calculated as a function of the concentration of MMC required to kill 50% of cells. The magnitude of sensitization achieved with 25 uM RI-1 was 2.5-3 fold, depending on the cell type. These data suggest that RI-1 can specifically interfere with RAD51 functions in human cancer cells, thereby rendering them more susceptible to the lethal effects of oncologic treatment[1].

Animal models

Female BALB/c nude mice (6 weeks)

Preparation Method

Mice bearing MDA-MB-157 xenografts with a tumor volume of 100mm3(±50), was then randomly grouped and treated by intraperitoneal injection every 3 days for 30 days with RI-1 (50 mg/kg), ABT888 (25 mg/kg), a combination of RI-1 and ABT888, or no treated. Tumors were taken 8 hours after last drug administration for immunofluorescence assay.

Dosage form

50 mg/kg,every 3 days for 30 days

Applications

The combination of ABT888 and RI-1 resulted in significant inhibition of tumor growth.The combination of ABT888 and RI-1 showed a slower growth and a decreased tumor weight of tumors.

产品描述

RI-1 is a RAD51 inhibitor, with IC50ranging from 5 to 30 μM. RI-1 binds covalently to the surface of RAD51 protein at cysteine 319. RI-1 inactivates RAD51 by directly binding to a protein surface that serves as an interface between protein subunits in RAD51 filaments. RI-1 can disrupt homologous recombination in human cells[1].RI-1 sensitizes cells to DNA damage by directly and specifically disrupting HsRAD51.RI-1covalently attaches to HsRAD51 protein, thereby inhibiting the ability of RAD51 to form filaments on ssDNA. RI-1 can inhibit sub-nuclear accumulation of HsRAD51 protein at sites of DNA damage, and this inhibitory activity sensitizes various cancer cell types to cross-linking chemotherapy[1].

In HeLa, MCF-7 and U2OS cells, RI-1 significantly sensitized cells to MMC. The magnitude of sensitization achieved with 25uM RI-1 was 2.5-3fold, depending on the cell type. These data suggest that RI-1 can specifically interfere with RAD51 functions in human cancer cells, thereby rendering them more susceptible to the lethal effects of oncologic treatment[1].In Huh7 and HCCLM3 cells,XRCC2 overexpression accelerates mtDNA level recovery, but treatment with RI-1 can deplete RAD51 and prevent mtDNA level recovery[3]. Rad51 inhibitor RI-1 to inhibit the HR in oocytes. 60 μM RI-1 exposure has no obvious effects on the PBE(polar body extrusion) rates of normal oocytes[4]. Ri-1 reduced γ-H2AX foci in G2 phase cells and resulted in elevated levels of unrepaired DNA double-strand breaks 6 hours after radiation[5].VS tumors expressed RAD51. VS may evade radiation injury by entering cell cycle arrest and upregulating RAD51-dependent repair of radiation-induced double-stranded breaks in DNA. Although there was variability in responses among individual primary VS cells, RAD51 inhibition with RI-1 reduced RAD51-dependent DNA repair to enhance radiation toxicity in VS cells[6]

In an MDA-MB-157 breast cancer model, mice were randomly assigned to one of four groups to receive vehicle, ABT888, RI-1, or combination of ABT888 and RI-1. The combination of ABT888 and RI-1 resulted in significant inhibition of tumor growth.The combination of ABT888 and RI-1 showed a slower growth and a decreased tumor weight of tumors[2]

References:
[1]. Budke B, Logan HL, et,al. RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells. Nucleic Acids Res. 2012 Aug;40(15):7347-57. doi: 10.1093/nar/gks353. Epub 2012 May 9. PMID: 22573178; PMCID: PMC3424541.
[2]. Shi Y, Jin J, et,al. DAXX, as a Tumor Suppressor, Impacts DNA Damage Repair and Sensitizes BRCA-Proficient TNBC Cells to PARP Inhibitors. Neoplasia. 2019 Jun;21(6):533-544. doi: 10.1016/j.neo.2019.04.001. Epub 2019 Apr 24. PMID: 31029033; PMCID: PMC6484230.
[3]. Zhao Z, He K, et,al. XRCC2 repairs mitochondrial DNA damage and fuels malignant behavior in hepatocellular carcinoma. Cancer Lett. 2021 Aug 1;512:1-14. doi: 10.1016/j.canlet.2021.04.026. Epub 2021 May 5. PMID: 33964350.
[4]. Ma JY, Feng X, et,al. The repair of endo/exogenous DNA double-strand breaks and its effects on meiotic chromosome segregation in oocytes. Hum Mol Genet. 2019 Oct 15;28(20):3422-3430. doi: 10.1093/hmg/ddz156. PMID: 31384951.
[5]. Bee L, Fabris S, et,al. The efficiency of homologous recombination and non-homologous end joining systems in repairing double-strand breaks during cell cycle progression. PLoS One. 2013 Jul 11;8(7):e69061. doi: 10.1371/journal.pone.0069061. PMID: 23874869; PMCID: PMC3708908.
[6]. Thielhelm TP, Nourbakhsh A, et,al. RAD51 Inhibitor and Radiation Toxicity in Vestibular Schwannoma. Otolaryngol Head Neck Surg. 2022 Mar 1:1945998221083506. doi: 10.1177/01945998221083506. Epub ahead of print. PMID: 35230908.