CAM833

• CAT Number: I042750
• CAS Number: 2758364-02-0
• Molecular Formula: C26H26ClFN4O5
• Molecular Weight: 528.96
• Purity: ≥95%
• Synonyms: N-[2-[(2S,4R)-2-[[(1S)-1-(2-chloro-4-methoxyphenyl)ethyl]carbamoyl]-4-hydroxypyrrolidin-1-yl]-2-oxoethyl]-6-fluoroquinoline-2-carboxamide
• InChI: InChI=1S/C26H26ClFN4O5/c1-14(19-6-5-18(37-2)11-20(19)27)30-26(36)23-10-17(33)13-32(23)24(34)12-29-25(35)22-7-3-15-9-16(28)4-8-21(15)31-22/h3-9,11,14,17,23,33H,10,12-13H2,1-2H3,(H,29,35)(H,30,36)/t14-,17+,23-/m0/s1
• InChIKey: PMUWBFKMLGLUTF-KNUWZQJKSA-N
• SMILES: CC(C1=C(C=C(C=C1)OC)Cl)NC(=O)C2CC(CN2C(=O)CNC(=O)C3=NC4=C(C=C3)C=C(C=C4)F)O

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. CAM833 increases the progression of G2/M-arrested cells into apoptosis[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 and suppresses extended RAD51 filament assembly[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 in HCT116 cells[1].
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[1].
CAM833 (20 μM; 96 h) potentiates the growth suppressive effect of PARP1 inhibition in BRCA2 wild-type cells[1].
CAM833 (96 h) alone inhibits the growth of HCT116 colon carcinoma cells with a GI50 (50% growth inhibition) of 38 μM, when combined with 3 Gy IR, CAM833 suppresses the growth of HCT116 cells with a GI50 of 14 μM[1].
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[1].

Reference

[1]. Scott DE, 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.
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