CAM833
目录号 : GC65935CAM833是一种亚微摩尔化学抑制剂，可抑制肿瘤抑制因子BRCA2的RAD51重组酶和BRC重复基序之间的调节蛋白相互作用。
Cas No.:2758364-02-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
HCT116 cell |
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Preparation Method |
HCT116 cells were treated with 20 μM CAM833 or DMSO, and exposure to 3gy ionizing radiation and the cell cycle was analyzed. |
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Reaction Conditions |
20 μM；72h |
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Applications |
CAM833 enhanced radiation-induced cell cycle arrest , increases the progression of G2/M-arrested cells into apoptosis in HCT116 cells. |
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References: [1]. Scott DE, Francis-Newton NJ, et,al. l-molecule inhibitor of the BRCA2-RAD51 interaction modulates RAD51 assembly and potentiates DNA damage-induced cell death. Cell Chem Biol. 2021 Jun 17;28(6):835-847.e5. doi: 10.1016/j.chembiol.2021.02.006. Epub 2021 Mar 3. PMID: 33662256; PMCID: PMC8219027. |
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CAM833, a sub-micromolar chemical inhibitor of the regulatory protein-protein interaction between the RAD51 recombinase and the BRC repeat motifs of the tumor suppressor BRCA2. CAM833 engages with two hydrophobic pockets on the surface of RAD51 that normally accommodate conserved hydrophobic side chains from the BRC repeats of BRCA2, thereby directly competing with the RAD51:BRCA2 interaction.CAM833 suppresses the assembly of RAD51 into damage-induced filaments, and impairs DNA repair by homologous DNA recombination. The Kd of CAM833 inhibiting ChimRAD51 is 366 nM [1]. CAM833 potentiates growth inhibition, cell-cycle arrest and cytotoxicity induced by DNA damage.
CAM833 (20 μM; 0-72 h) enhanced radiation-induced cell cycle arrest in HCT116 cells and increased apoptosis over time, CAM833 also enhanced the inhibition of PARP1 in HCT116 cells [1].
References:
[1]. Scott DE, Francis-Newton NJ, et,al. A small-molecule inhibitor of the BRCA2-RAD51 interaction modulates RAD51 assembly and potentiates DNA damage-induced cell death. Cell Chem Biol. 2021 Jun 17;28(6):835-847.e5. doi: 10.1016/j.chembiol.2021.02.006. Epub 2021 Mar 3. PMID: 33662256; PMCID: PMC8219027.
CAM833是一种亚微摩尔化学抑制剂，可抑制肿瘤抑制因子BRCA2的RAD51重组酶和BRC重复基序之间的调节蛋白相互作用。CAM833与RAD51表面的两个疏水口袋接合，通常容纳来自BRCA2的BRC重复序列的保守疏水侧链，从而直接与RAD51:BRCA2相互作用竞争。CAM833抑制RAD51在损伤诱导丝中的组装，并通过同源DNA重组损害DNA修复。此外，CAM833抑制ChimRAD51蛋白的Kd为366 nM[1]。CAM833增强了DNA损伤诱导的生长抑制、细胞周期阻滞和细胞毒性。
CAM833 (20 μM; 0-72 h) 在 HCT116 细胞中增强辐射诱导的细胞周期阻滞，并随时间增加细胞凋亡，CAM833 也增强 HCT116 细胞 中 PARP1 的抑制作用[1]。
| Cas No. | 2758364-02-0 | SDF | Download SDF |
| 分子式 | C26H26ClFN4O5 | 分子量 | 528.96 |
| 溶解度 | DMSO : 100 mg/mL | 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 | 1.8905 mL | 9.4525 mL | 18.905 mL |
| 5 mM | 0.3781 mL | 1.8905 mL | 3.781 mL |
| 10 mM | 0.1891 mL | 0.9453 mL | 1.8905 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。
A small-molecule inhibitor of the BRCA2-RAD51 interaction modulates RAD51 assembly and potentiates DNA damage-induced cell death
Cell Chem Biol 2021 Jun 17;28(6):835-847.e5.PMID:33662256DOI:PMC8219027
BRCA2 controls RAD51 recombinase during homologous DNA recombination (HDR) through eight evolutionarily conserved BRC repeats, which individually engage RAD51 via the motif Phe-x-x-Ala. Using structure-guided molecular design, templated on a monomeric thermostable chimera between human RAD51 and archaeal RadA, we identify CAM833, a 529 Da orthosteric inhibitor of RAD51:BRC with a Kd of 366 nM. The quinoline of CAM833 occupies a hotspot, the Phe-binding pocket on RAD51 and the methyl of the substituted α-methylbenzyl group occupies the Ala-binding pocket. In cells, CAM833 diminishes formation of damage-induced RAD51 nuclear foci; inhibits RAD51 molecular clustering, suppressing extended RAD51 filament assembly; potentiates cytotoxicity by ionizing radiation, augmenting 4N cell-cycle arrest and apoptotic cell death and works with poly-ADP ribose polymerase (PARP)1 inhibitors to suppress growth in BRCA2-wildtype cells. Thus, chemical inhibition of the protein-protein interaction between BRCA2 and RAD51 disrupts HDR and potentiates DNA damage-induced cell death, with implications for cancer therapy.