Description
CAM833 is a potent orthosteric inhibitor of the interaction between BRCA2 and RAD51 with a K d of 366 nM against the ChimRAD51 protein. CAM833 also inhibits RAD51 oligomerization. CAM833 increases the progression of G2/M-arrested cells into apoptosisIn VitroCAM833 (3.125-50 µM; 24 h) causes a concentration-dependent decrease in RAD51 foci and subsequent increase in DNA damage. CAM833 (25 µM) inhibits RAD51 molecular clustering at DNA damage sites and suppresses extended RAD51 filament assembly. CAM833 (0-50 µM) inhibits DNA repair by homologous recombination. CAM833 (20 µM; 0-72 h) potentiates radiation-induced cell-cycle arrest and increases apoptosis over time in HCT116 cells. CAM833 (0.1-100 µM; 96 h) causes a dose-dependent growth inhibition of multiple cancer-derived human cell lines that is enhanced when combined with ionizing radiation. CAM833 (20 µM; 96 h) potentiates the growth suppressive effect of PARP1 inhibition in BRCA2 wild-type cells. CAM833 (96 h) alone inhibits the growth of HCT116 colon carcinoma cells with a GI 50 (50% growth inhibition) of 38 µM, when combined with 3 Gy IR, CAM833 suppresses the growth of HCT116 cells with a GI 50 of 14 µM. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Cycle AnalysisCell 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.Form:SolidIC50& Target:K d : 355 nM (ChimRAD51, measured by FP), 366 nM (ChimRAD51, measured by ITC)