homologous recombination

Ran-IN-1 (Compound M36) is an orally active and selective inhibitor of Ran GTPase. It binds allosterically with high specificity to the switch II pocket of GDP-bound Ran (RanGDP), stabilizing its inactive state and reducing the formation of active Ran-GTP. Ran-IN-1 induces apoptosis in epithelial ovarian cancer (EOC) cells and inhibits DNA repair pathways such as homologous recombination (HR) and non-homologous end joining (NHEJ). This compound shows potential for research in epithelial ovarian cancer, particularly in high-grade serous carcinoma.

D-G23 is a selective RAD52 inhibitor. It disrupts RAD52-mediated DNA repair pathways and suppresses the growth of cancer cells deficient in BRCA1 and BRCA2. D-G23 shows promise for research into homologous recombination-related cancers caused by BRCA1/2 mutations, such as hereditary breast and ovarian cancers.

BRCA2-RAD51-IN-2 (compound S-35d) is a BRCA2-RAD51 inhibitor that, when combined with 10 µM Olaparib, can inhibit homologous recombination repair.

RI-1 (RAD51 inhibitor 1) is a RAD51 inhibitor (IC50: 5-30 μM).

RI-2 is an optimized RAD51 inhibitor with an IC50 of 44.17 μM in the standard DNA binding assay; specifically inhibits HR(Homologous recombination) repair in human cells.

RI(dl)-2 TFA is a potent and selective inhibitor of RAD51-mediated D-loop formation, with an IC50 of 11.1 μM, and inhibits homologous recombination (HR) activity in human cells with an IC50 of 3.0 μM [1].

CAY10760 is an inhibitor of the protein-protein interaction between RAD51 recombinase and BRCA2 (EC50= 19 μM in a cell-free competitive ELISA).1It decreases homologous recombination by 54% in wild-typeBRCA2-expressing BxPC-3 pancreatic cancer cells when used at a concentration of 20 μM. CAY10760 (20 μM) decreases proliferation of BxPC-3, as well as mutantBRCA2-expressing Capan-1, cancer cells when used alone or in combination with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib . 1.Bagnolini, G., Milano, D., Manerba, M., et al.Synthetic lethality in pancreatic cancer: Discovery of a new RAD51-BRCA2 small molecule disruptor that inhibits homologous recombination and synergizes with olaparibJ. Med. Chem.63(5)2588-2619(2020)

Simmiparib (SMOCL-9112) is a novel and potent PARP1 and PARP2 inhibitor, a derivative of Olaparib.Simmiparib induces DNA double-strand breaks (DSBs) and cell cycle arrest in homologous recombination repair (HR)-deficient cells, thereby contributing to apoptosis.Simmiparib has been used for study Parkinson's disease, Alzheimer's disease, breast cancer, and melanoma.

MI-223 is an inhibitor of Mcl-1-stimulated homologous recombination (HR) DNA repair, which leads to sensitization of cancer cells to hydroxyurea- or olaparib-induced DNA replication stress.

PU-H71 HCl (Zelavespib HCl) is a novel Hsp90 inhibitor, a novel purine-based analog, and a radiosensitizer that may be a promising agent for CIRT. PU-H71 HCL shows antitumor activity in many preclinical models of malignancy. PU-H71 HCL has an inhibitory effect on the protein expression levels of Rad51 and Ku70, which may be associated with the double chain break repair in the homologous recombination pathway and non-homologous end-joining pathway.

Antitumor agent-81, a P62-RNF168 agonist with low cytotoxicity, enhances the P62-RNF168 interaction, leading to decreased RNF168-mediated H2A ubiquitination and impaired homologous recombination-mediated DNA repair. Additionally, it exhibits dose-dependent inhibition of xenograft tumor growth in mice.

NHEJ Inhibitor-1 (Compound C2), a trifunctional Pt(II) complex, mitigates non-homologous end joining (NHEJ) homologous recombination (HR)-related double strand break (DSB) repairs, combating Cisplatin resistance in non-small cell lung cancer (NSCLC). It achieves this by inhibiting the damage repair proteins Ku70 and Rad51, thus re-sensitizing tumors to Cisplatin. Additionally, this compound prompts the generation of reactive oxygen species (ROS) and reduces mitochondrial membrane potential (MMP) [1].

Antitumor agent-96 (Compound D34) is a potent MRE11 inhibitor that down-regulates the homologous recombination (HR) pathway by binding to and suppressing the endonuclease functions of MRE11, thereby inducing apoptosis in CM cells [1].

Fluzoparib (SHR3162) is a novel, potent, and orally available inhibitor of PARP, potentially for the treatment of solid tumours.

PFM01 is an inhibitor of MRE11 endonuclease. PFM01 can regulate double-strand break repair (DSBR) by nonhomologous end-joining (NHEJ) versus homologous recombination (HR).

AZD-9574 is a selective inhibitor of PARP1 at the sites of SSBs. AZD-9574 exhibits anti-cancer activities and can be used in studies about HRD+ breast cancer and advanced solid malignancies.

KWWCRW is an inhibitory peptide targeting the Holliday junction, exhibiting anticancer activity. It inhibits homologous recombination repair (HDR) during DNA repair by binding to the intermediate structures of the reactive Holliday junction and preventing their resolution. Additionally, KWWCRW inhibits site-specific recombination in vitro in bacteriophages.