dna double-strand break

Mirin is a Mre11-Rad50-Nbs1 (MRN) complex inhibitor that inhibits MRN-dependent ATM activation without affecting ATM protein kinase activity. It also inhibits Mre11-associated exonuclease activity, thereby disrupting DNA double-strand break repair.Mirin induces cell cycle arrest in G1 phase.

VX-984 (M9831) is an oral, selective DNA-PK inhibitor that can cross the blood-brain barrier. VX-984 inhibited the conjugation of non-homologous terminal NHEJ and acted on DSBs to break DNA double strand. VX-984 is commonly seen in glioblastoma (GBM) and non-small cell lung cancer (NSC-LC) studies.

IBR2 (Isoquinoline) is a potent and specific RAD51 inhibitor known for its ability to suppress RAD51-mediated DNA double-strand break repair. By interfering with RAD51 multimerization, accelerating proteasome-mediated RAD51 protein degradation, inhibiting cancer cell growth, and inducing apoptosis, IBR2 has proved to be an effective compound in these aspects.

SU-11752 is a potent and selective DNA-PK inhibitor. Inhibition kinetics and a direct assay for ATP binding showed that SU11752 inhibited DNA-PK by competing with ATP. SU11752 inhibited DNA double-strand break repair in cells and gave rise to a five-fold sensitization to ionizing radiation. At concentrations of SU11752 that inhibited DNA repair, cell cycle progression was still normal and ATM kinase activity was not inhibited.

PARP-1-IN-13 (Compound 19c) is a potent PARP-1 inhibitor with an IC50 of 26 nM, hindering DNA single-strand break repair and exacerbating double-strand breaks, leading to apoptosis in cancer cells via the mitochondrial pathway [1].

T2AA, a proliferating cell nuclear antigen (PCNA) inhibitor, disrupts protein-protein interactions between PCNA and both a PIP-box-containing peptide (IC50= 1 μM) and full-length p21, reducing cellular colocalization of PCNA with DNA polymerase δ. This compound effectively inhibits DNA replication and cell proliferation in U2OS and HeLa cells in a concentration-dependent manner, additionally inducing S phase cell cycle arrest at a 20 μM concentration. Furthermore, T2AA enhances DNA double strand break formation alongside cisplatin in a neutral comet assay and augments cisplatin-induced reductions in clonogenic survival in HeLa and U2OS cells.

IC 86621 is a selective and reversible ATP-competitive inhibitor of DNA-PK with an IC50 of 120 nM. IC 86621 increases DNA double-strand break(DSB)-induced antitumor activity with an EC50 of 68 µM for DNA-PK mediated cellular DSB repair.