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RAD51 inhibitors and modulators act on the recombinase at the center of homologous recombination repair. RAD51 is the human counterpart of bacterial recombination protein A (RecA) and repairs DNA double-strand breaks by copying an intact template. It coats single-stranded DNA as a helical filament, and purified human RAD51 carries out ATP-dependent homologous pairing and strand exchange. Breast cancer susceptibility protein 2 (BRCA2) loads RAD51 onto DNA through eight short repeat motifs. RAD51 Inhibitor B02 came from a high-throughput screen for compounds that block RAD51 strand exchange. RI-1 and IBR2 are further RAD51 inhibitors, while CAM833 disrupts the BRCA2-RAD51 interaction. RS-1 works in the opposite direction and stimulates the recombination activity of RAD51.
Synonyms: RI1?? RI 1
RI-1 is a small molecule that inhibits the central recombination protein RAD51. RI-1 specifically reduces gene conversion in human cells while stimulating single strand annealing. RI-1 binds covalently to the surface of RAD51 protein at cysteine 319 that likely destabilizes an interface used by RAD51 monomers to oligomerize into filaments on DNA.
Synonyms: B02; RAD51-IN-02
AD51 Inhibitor B02 (B02) is an inhibitor of human RAD51 with an IC50 of 27.4 μM.
RAD51-IN-2 (compound example 67A) is a RAD51 inhibitor extracted from patent WO2019/051465A1.
RI-2 is a reversible RAD51 inhibitor, with an IC50 of 44.17 μM, and specifically inhibits homologous recombination repair in human cells.
Bractoppin is a potent and selective inhibitor of phosphopeptide recognition by the BRCA1 tBRCT domain.
CAM833 is a potent orthosteric inhibitor of the BRCA2-RAD51 interaction, exhibiting a Kd of 366 nM against ChimRAD51 protein. This compound also disrupts RAD51 oligomerization, leading to enhanced progression of G2/M-arrested cells into apoptosis. CAM833 is valuable for research applications aimed at studying DNA repair mechanisms and therapeutic strategies in BRCA2-related cancers.
Homologous recombination-IN-1 is an inhibitor of the RAD51-BRCA2 protein-protein interaction, demonstrating an EC50 of 19 μM. This compound effectively disrupts homologous recombination processes, making it a valuable tool for studying DNA repair mechanisms and the underlying biology of cancer. Researchers can utilize Homologous recombination-IN-1 to investigate the roles of RAD51 and BRCA2 in genetic stability and therapeutic responses.
RAD51-IN-1 is a selective inhibitor of the RAD51 protein, which is crucial for homologous recombination and DNA repair processes. This compound has demonstrated significant anti-tumor activity and may be utilized in cancer research to explore its potential in enhancing the effectiveness of cancer therapies by targeting DNA repair mechanisms. Its application may also extend to investigations of DNA damage response pathways and their implications in cancer biology.
RAD51-IN-5 is a selective inhibitor of RAD51, a key protein involved in homologous recombination repair of DNA double-strand breaks. This compound demonstrates potential in exploring therapeutic strategies for conditions associated with mitochondrial defects. Its activity against RAD51 may provide insights into DNA repair mechanisms and related cellular processes in various research applications.
RAD51-IN-3 is a potent inhibitor of the RAD51 protein, which plays a crucial role in homologous recombination and DNA repair mechanisms. By targeting RAD51, this compound interferes with DNA damage response pathways, making it valuable for research in cancer biology, particularly in exploring therapeutic strategies that exploit DNA repair deficiencies. Its application extends to studies investigating the sensitivity of tumor cells to chemotherapeutic agents and the development of novel cancer treatment modalities.
RAD51-IN-4 is a potent inhibitor of the RAD51 protein, essential for homologous recombination and DNA repair in eukaryotic cells. This compound demonstrates significant anti-proliferative activity and has potential applications in studying conditions associated with mitochondrial defects and genomic stability. Researchers may utilize RAD51-IN-4 to explore cancer biology, therapeutic resistance, and the underlying mechanisms of DNA repair processes.
RAD51-IN-7 is a selective inhibitor of RAD51, a key protein involved in homologous recombination and DNA repair mechanisms in eukaryotic cells. This compound is valuable for investigating conditions associated with mitochondrial dysfunction and its role in cancer biology. The potential applications of RAD51-IN-7 extend to studies targeting cellular responses to genotoxic stress and the development of therapeutic strategies for genetic diseases.
RAD51-IN-6 is a highly effective inhibitor of RAD51, a key protein involved in homologous recombination and DNA repair in eukaryotic cells. This compound demonstrates significant biological activity by interfering with RAD51-mediated processes, making it a valuable tool for studying conditions related to mitochondrial defects and other genomic instability disorders. Its application in research may provide insights into therapeutic strategies targeting RAD51-related pathways.
(R)-IBR2 is the isomer of IBR2, serving as a potent and specific inhibitor of RAD51. By disrupting RAD51 multimerization and enhancing proteasome-mediated degradation of RAD51 protein, (R)-IBR2 effectively inhibits DNA double-strand break repair. Its biological activity has implications in cancer research, demonstrating the ability to inhibit cancer cell growth and induce apoptosis.
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RI(dl)-2 is a potent inhibitor of RAD51, specifically targeting its D-loop activity with an IC50 of 11.1 µM, and effectively inhibiting homologous recombination (HR) with an IC50 of 3.0 µM. This compound disrupts HR-mediated repair of DNA double-strand breaks, leading to increased sensitivity in various cancer cell lines. RI(dl)-2 serves as a valuable tool for investigating HR processes and exploring potential therapeutic strategies in cancer research.
Synonyms: MDL101114ZA free base
DIDS is a RAD51 inhibitor that disrupts RAD51-mediated homologous pairing and strand exchange reactions, thereby impacting DNA repair processes. In addition to its primary function, DIDS also inhibits ABCA1 and VDAC1, affecting anion exchange and binding to red blood cell membranes. Furthermore, it has been shown to inhibit the activation of caspase-3 and -9, making it a valuable tool for cancer research applications.
RAD51-IN-9 is a potent inhibitor of RAD51, effectively disrupting the binding of RAD51 to single-stranded DNA with an IC50 of 17.85 μM. This compound demonstrates an LD50 against HEK293 cells of 40.21 μM and is capable of sensitizing cells to the cytotoxic effects of Mitomycin C. RAD51-IN-9 is a valuable tool for research focused on DNA repair mechanisms and the therapeutic targeting of cancer cells.
BRCA2-RAD51-IN-1 is a specific inhibitor of the BRCA2-RAD51 complex, demonstrated to have an EC50 value of 28 μM. This compound exhibits notable antitumor activity, making it a valuable tool for research into cancer treatments targeting DNA repair mechanisms. Its application in studies of BRCA-mediated tumorigenesis helps elucidate potential therapeutic strategies for cancers associated with BRCA2 mutations.
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