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]。