IBR2
目录号 : GC32912
IBR2是一种特异性RAD51抑制剂。
Cas No.:313526-24-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >97.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment: |
Human breast cancer cell lines MCF7, MDA-MB-231, MDA-MB-361, MDA-MB-435, MDA-MB468, Hs578-T, human osteosarcoma cell line U20S, human glioblastoma cell line T98G and human cervical adenocarcinoma cell line HeLa are used. Standard XTT assays with a four-day drug treatment procedure are performed to measure the dose dependent cytotoxicity of IBR analogs in cultured cells. In brief, cells are plated on 96-well dishes one day before the drug treatment, followed by drug (e.g., IBR2) treatment on day 2 and XTT assay on day 6 after drug addition by using a commercial cell proliferation kit . Triplicate sets are measured and compiled for final data presentation[1]. |
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References: [1]. Zhu J, et al. Synthesis, molecular modeling, and biological evaluation of novel RAD51 inhibitors. Eur J Med Chem. 2015;96:196-208. |
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IBR2 is a specific RAD51 inhibitor.
IBR2 shows interesting RAD51 inhibition activities. RAD51 is rapidly degraded in IBR2-treated cancer cells, and the homologous recombination repair is impaired, subsequently leading to cell death. The IC50 values of the original IBR2 are in the range of 12-20 µM for most tested cancer cell lines. IBR2 can inhibit the growth of triple-negative human breast cancer cell line MBA-MD-468 with an IC50 of 14.8 µM[1].
[1]. Zhu J, et al. Synthesis, molecular modeling, and biological evaluation of novel RAD51 inhibitors. Eur J Med Chem. 2015;96:196-208.
| Cas No. | 313526-24-8 | SDF | |
| Canonical SMILES | O=S(N1C(C2=CNC3=C2C=CC=C3)C4=C(C=CC=C4)C=C1)(CC5=CC=CC=C5)=O | ||
| 分子式 | C24H20N2O2S | 分子量 | 400.49 |
| 溶解度 | DMSO : ≥ 150 mg/mL (374.54 mM) | 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 | 2.4969 mL | 12.4847 mL | 24.9694 mL |
| 5 mM | 0.4994 mL | 2.4969 mL | 4.9939 mL |
| 10 mM | 0.2497 mL | 1.2485 mL | 2.4969 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。
Stereoselective synthesis of chiral IBR2 analogues
J Org Chem 2009 Mar 6;74(5):2018-27.PMID:19191556DOI:10.1021/jo802607f.
Two stereoselective routes were developed to synthesize optically pure IBR2 analogues 1-16. The first features addition of N-Boc-3-bromoindole 26 to the sulfinamide 25, providing a 1:1 ratio of the separable diasteroisomers 27 and 28 in good yield. In a straightforward fashion, the sulfinamides 27 and 28 were conveniently converted into the key amines 39 and 47 over 8 steps, respectively, from which a series of 3,4-dihydroisoquinolinyl IBR2 analogues 1-14 containing fluorinated and trifluoromethylated benzyl groups were prepared. Another route highlights the highly enantioselective addition of indole to the sulfonyl amide 50 with bifunctional aminothioureas 57 and 58 as catalysts. After the reaction conditions were optimized, the desired sulfonyl amides (R)-55 and (S)-55 were obtained in 99% ee and 98% ee, respectively. Acylation of (R)-55 and (S)-55 separately and subsequent allylation gave compounds 60 and 63, respectively, which were further subjected to RCM to furnish compounds 61 and 64 and, after removal of the Boc groups, the desired IBR2 analogues 15 and 16.
Synergistic Antiproliferative Activity of the RAD51 Inhibitor IBR2 with Inhibitors of Receptor Tyrosine Kinases and Microtubule Protein
J Pharmacol Exp Ther 2018 Jan;364(1):46-54.PMID:29061656DOI:10.1124/jpet.117.241661.
Although cancer cell genetic instability contributes to characteristics that mediate tumorigenicity, it also contributes to the tumor-selective toxicity of some chemotherapy drugs. This synthetic lethality can be enhanced by inhibitors of DNA repair. To exploit this potential Achilles heel, we tested the ability of a RAD51 inhibitor to potentiate the cytotoxicity of chemotherapy drugs. 2-(Benzylsulfonyl)-1-(1H-indol-3-yl)-1,2-dihydroisoquinoline (IBR2) inhibits RAD51-mediated DNA double-strand break repair but also enhances cytotoxicity of the Bcr-Abl inhibitor imatinib. The potential for synergy between IBR2 and more drugs was examined in vitro across a spectrum of cancer cell lines from various tissues. Cells were exposed to IBR2 simultaneously with inhibitors of receptor tyrosine kinases, DNA-damaging agents, or microtubule disruptors. IBR2, at concentrations that inhibited proliferation between 0% and 75%, enhanced toxicity by up to 80% of imatinib and regorafenib (targets RAF and kit); epidermal growth factor receptor inhibitors erlotinib, gefitinib, afatinib, and osimertinib; and vincristine, an inhibitor of microtubule function. However, IBR2 antagonized the action of olaparib, cisplatin, melphalan, and irinotecan. A vincristine-resistant squamous cell line was not cross resistant to imatinib, but IBR2 and another RAD51 inhibitor (B02) enhanced imatinib toxicity in this cell line, its HN-5a parent, and the colon cancer line HT-29 by up to 60% and much better than verapamil, a P-glycoprotein inhibitor (P < 0.05). Given the disparate agents the functions of which are enhanced by IBR2, the mechanisms of enhancement may be multimodal. Whether RAD51 is common to these mechanisms remains to be elucidated, but it provides the potential for selectivity to tumor cells.
A High-Performance Quasi-Solid-State Aqueous Zinc-Dual Halogen Battery
ACS Nano 2022 Dec 27;16(12):20389-20399.PMID:36512756DOI:10.1021/acsnano.2c06362.
Aqueous zinc-based batteries are promising candidates for the grid-scale energy storage owing to their nonflammability, ecofriendliness, and low cost. Nevertheless, their practical applications are hindered by the relatively low capacity and energy density. Herein, we develop a quasi-solid-state aqueous zinc-dual halogen battery composed of freestanding carbon cloth-iodine cathode and in situ prepared concentrated aqueous gel electrolyte. The freestanding composite cathode and aqueous gel electrolyte can afford iodine source and bromide ions, respectively, thus activating the I-/I0/I+ reaction by forming [IBR2]- interhalogen. Furthermore, the conversion reaction of Br-/Br0 in [IBR2]- interhalogen is stimulated due to the catalytic effect of iodine. Therefore, this rationally designed aqueous dual halogen conversion chemistry enables three successive redox reactions (i.e., I-/I0, I0/I+, and Br-/Br0). Additionally, the LiNO3 additive and acrylamide (AM)-based polymer matrix not only stabilizes the anode/electrolyte interface but also restrains the side reactions and dissolution/diffusion of active species. Consequently, the as-assembled aqueous zinc-dual halogen battery exhibits high areal capacity and energy density.
A novel small molecule RAD51 inactivator overcomes imatinib-resistance in chronic myeloid leukaemia
EMBO Mol Med 2013 Mar;5(3):353-65.PMID:23341130DOI:10.1002/emmm.201201760.
RAD51 recombinase activity plays a critical role for cancer cell proliferation and survival, and often contributes to drug-resistance. Abnormally elevated RAD51 function and hyperactive homologous recombination (HR) rates have been found in a panel of cancers, including breast cancer and chronic myeloid leukaemia (CML). Directly targeting RAD51 and attenuating the deregulated RAD51 activity has therefore been proposed as an alternative and supplementary strategy for cancer treatment. Here we show that a newly identified small molecule, IBR2, disrupts RAD51 multimerization, accelerates proteasome-mediated RAD51 protein degradation, reduces ionizing radiation-induced RAD51 foci formation, impairs HR, inhibits cancer cell growth and induces apoptosis. In a murine imatinib-resistant CML model bearing the T315I Bcr-abl mutation, IBR2, but not imatinib, significantly prolonged animal survival. Moreover, IBR2 effectively inhibits the proliferation of CD34(+) progenitor cells from CML patients resistant to known BCR-ABL inhibitors. Therefore, small molecule inhibitors of RAD51 may suggest a novel class of broad-spectrum therapeutics for difficult-to-treat cancers.
Halogen Radical Chemistry at Aqueous Interfaces
J Phys Chem A 2016 Aug 11;120(31):6242-8.PMID:27414750DOI:10.1021/acs.jpca.6b04219.
Halogens play key roles in the chemical composition of marine boundary layers, the free troposphere and the stratosphere. Atmospheric halogen chemistry is dominated by reactions between gas-phase and aqueous species on the surfaces of the ocean and marine aerosol. The mechanisms of interfacial halogen radical/halide reactions, however, are not fully understood, partly due to the dearth of techniques for in situ monitoring of the products and intermediates of fast interfacial halogen radical reactions. Here, we report the online electrospray mass spectrometric identification of the species produced on the surface of aqueous Br(-) and I(-) microjets collided by I(•)(g) pulses generated from the 266 nm laser photolysis of CH3I/O2/N2 gas mixtures. Mass-specific identification of intermediates and products in D2O and H2(18)O solutions and their dependences on I(•)(g) fluxes let us outline mechanisms of formation. We found that the uptake of I(•)(g) on the surface of Br(-) and I(-) microjets (effective uptake coefficient γeff ≥ 2 × 10(-4)) yields IBr(•)(-)/I2(•)(-) radical intermediates, which rapidly react with additional I(•) to produce trihalides I2Br(-)/IBR2(-)/I3(-) plus I3On(-) (n = 1, 2) species within ∼10 μs. Our findings point to a new halogen activation pathway initiated by photogenerated I(•).