CAM833
目录号 : GC65935CAM833 是一种有效的抑制 BRCA2 和 RAD51 之间相互作用的正位抑制剂,对 ChimRAD51 蛋白的 Kd 为 366 nM。 CAM833 也抑制 RAD51 的寡聚。
Cas No.:2758364-02-0
Sample solution is provided at 25 µL, 10mM.
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- Purity: >99.50%
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CAM833 is a potent orthosteric inhibitor of the interaction between BRCA2 and RAD51 with a Kd of 366 nM against the ChimRAD51 protein. CAM833 also inhibits RAD51 oligomerization[1].
CAM833 (3.125-50 μM; 24 h) causes a concentration-dependent decrease in RAD51 foci and subsequent increase in DNA damage[1].
CAM833 (25 μM) inhibits RAD51 molecular clustering at DNA damage sites[1].
CAM833 (0-50 μM) inhibits DNA repair by homologous recombination[1].
CAM833 (20 μM; 0-72 h) potentiates radiation-induced cell-cycle arrest and increases apoptosis over time[1].
CAM833 (10 μM) causes a dose-dependent growth inhibition that is enhanced when combined with ionizing radiation[1].
CAM833 (20 μM; 96 h) potentiates the growth suppressive effect of PARP1 inhibition in BRCA2 wild-type cells[1].
Cell Cycle Analysis[1]
Cell Line: | HCT116 cells |
Concentration: | 20 μM |
Incubation Time: | 0-72 h |
Result: | In the control the percentage of cells in the apoptotic subG1 fraction remains below 5% throughout, in the compound-treated cells this rises progressively to peak at 15% at 48 hours. |
Cas No. | 2758364-02-0 | SDF | Download SDF |
分子式 | C26H26ClFN4O5 | 分子量 | 528.96 |
溶解度 | 储存条件 | Store at -20°C | |
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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) | ||||||||||
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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。
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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.