RI-2
目录号 : GC12752
A RAD51 inhibitor
Cas No.:1417162-36-7
Sample solution is provided at 25 µL, 10mM.
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Description:
IC50: 44.17 μM
Homologous recombination (HR) is an essential process in cells that provides repair of DNA double-strand breaks and lesions that block DNA replication. RAD51 is an evolutionarily conserved protein that is central to HR. Overexpression of RAD51 protein is common in cancer cells and represents a potential therapeutic target in oncology. RI-2 is an optimized reversible RAD51 inhibitor.
In vitro: Although RI-2 did exhibit reduced activity relative to RI-1, it did retain enough activity to sensitize cells to MMC cell-based assays. RI-2 exhibited no reactivity toward glutathione after incubation for 24 hours. RAD51 protein that had been treated with RI-2 prior to washing exhibited no measurable loss of DNA binding activity, even though RI-2 is known to inhibit RAD51 with an IC50 of 44.17 μM. This indicates that RAD51 inhibition by RI-2 is fully reversible [1].
In vivo: RI-1, the analogue of RI-2, facilitated mapping of the binding pocket within known crystal structures of RAD51. However, this reactivity of RI-1 potentially may limit its development in pre-clinical animal models. RI-1 has been found to exhibit a relatively short half-life, due to reactivity in thiol-containing solutions [1].
Clinical trial: Up to now, RI-2 is still in the preclinical development stage.
Reference:
[1] Budke B, Kalin JH, Pawlowski M, Zelivianskaia AS, Wu M, Kozikowski AP, Connell PP. An optimized RAD51 inhibitor that disrupts homologous recombination without requiring Michael acceptor reactivity. J Med Chem. 2013 Jan 10;56(1):254-63.
Cell experiment: | HEK293 cells are plated into 96-well tissue culture plates at a density of 300 cells per well in the presence or absence of 50 nM mitomycin C (MMC) for 24 hours at 37°C, 5% CO2. Media is subsequently replaced with fresh media containing 0.5% DMSO plus RI-2 for an additional 24 hours. RI-2 is then removed, and cultures are allowed to grow to a 50-70% confluence. Average survival from at least three replicates is measured using CellGlo reagentor. RI-2 is deemed successful in sensitizing cells to MMC if they generate significantly greater toxicity in the presence of MMC relative to the absence of MMC. Specifically, sensitization is scored as a “+” when non-overlapping standard errors are observed for at least two pairs of compound doses[1]. |
References: [1]. Budke B, et al. An optimized RAD51 inhibitor that disrupts homologous recombination without requiring Michael acceptor reactivity. J Med Chem. 2013 Jan 10;56(1):254-63. | |
| Cas No. | 1417162-36-7 | SDF | |
| 化学名 | 1-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)-4-morpholino-1H-pyrrole-2,5-dione | ||
| Canonical SMILES | COC1=CC=C(C(C(N2C3=CC(Cl)=C(Cl)C=C3)=O)=C(N4CCOCC4)C2=O)C=C1 | ||
| 分子式 | C21H18Cl2N2O4 | 分子量 | 433.28 |
| 溶解度 | ≥ 21.65mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.308 mL | 11.5399 mL | 23.0798 mL |
| 5 mM | 0.4616 mL | 2.308 mL | 4.616 mL |
| 10 mM | 0.2308 mL | 1.154 mL | 2.308 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet