double-strand

LJI308 is a potent, and pan-RSK (p90 ribosomal S6 kinase) inhibitor with IC50 of 6 nM, 4 nM, and 13 nM for RSK1, RSK2, and RSK3, respectively.

Irinotecan (CPT-11), a derivative of camptothecin, is an inhibitor of DNA topoisomerase I (Topo I). Irinotecan has antitumor activity by preventing DNA strand reattachment through binding to the Topo I complex, resulting in double-stranded DNA breaks and cell death.

Zelpolib is a specific inhibitor of DNA polymerase δ (Pol δ), thereby inhibiting DNA replication and DNA double-strand break homologous recombination repair. It exhibits antiproliferative activity in triple-negative breast cancer cell lines, pancreatic cancer cell lines, and platinum-resistant pancreatic cancer cell lines.

UNC-2170 (UNC2170 Maleate) is the methyl-lysine binding protein, 53BP1 ligand.

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.

Methylproamine is a DNA-binding radioprotector that acts by repairing transient radiation-induced oxidative species on DNA.

Calicheamicin (Calicheamicin γ1) is an antitumor antibiotic and is a DNA synthesis inhibitor. It also is a cytotoxic agent that causes double-strand DNA breaks.

Neocarzinostatin is an effective DNA-damaging, anti-tumor antibiotic. It recognizes double-stranded DNA bulge and induces DNA double strand breaks (DSBs). Neocarzinostatin leads to apoptosis. Neocarzinostatin has potential for EpCAM-positive cancer treatment.

5-BrdUTP sodium salt is a TdT substrate used for labeling DNA double-strand breaks.

XSJ05, a derivative of camptothecin (CPT), exhibits anti-cancer activity by inhibiting topoisomerase I (Topo I). This compound induces DNA double-strand breaks, leading to DNA damage. Furthermore, XSJ05 stifles the growth of colorectal cancer (CRC), halts the cell cycle in the G2/M phase, and induces apoptosis.

PARP1-IN-27 (Compound 9B) serves as an inhibitor of both PARP1 and PARP2, exhibiting IC 50 values of 2.53 nM and 6.45 nM, respectively, in SUM149PT cells. This compound effectively suppresses the proliferation of BRCA-mutated cancer cell lines such as SUM149PT, HCC1937, and Capan-1, with respective IC 50 values of 0.62, 1.91, and 4.26 μM. Additionally, PARP1-IN-27 exacerbates DNA double-strand breaks, enhances ROS production, causes G2/M phase cell cycle arrest, and triggers apoptosis in SUM149PT cells.

GSK_WRN4 is a WRN helicase inhibitor with anticancer activity. It induces DNA double-strand breaks and inhibits MSI tumor cell growth, making it useful in cancer research.

AcBut-N-Ac-γ-Calicheamicin serves as a toxic molecule for ADCs, inducing cell cycle arrest and apoptosis (Apoptosis) by causing DNA double-strand breaks. Primarily utilized in the synthesis of antibody-drug conjugates (ADC), it holds promise for cancer research, particularly in studies related to acute lymphoblastic leukemia (ALL) and other hematological malignancies.

Tilatamig samrotecan (AZD9592) is an antibody-drug conjugate (ADC) designed to deliver a topoisomerase I inhibitor (TOP1i). It targets epidermal growth factor receptor (EGFR) and c-MET and demonstrates antitumor activity. The compound induces DNA double-strand breaks, elevates pRAD50 and γH2AX expression, and inhibits the growth of non-small cell lung cancer.

MU147 is an MRE11 nuclease inhibitor and chemical probe with anticancer properties, exhibiting lethal effects on Ehrlich ascites tumor cells both in vivo and in vitro. It disrupts the MRE11 nuclease-dependent double-strand break repair mechanism without impairing ATM activation. Additionally, MU147 damages the degradation of nascent strands at stalled replication forks and selectively affects BRCA2-deficient cells.

HDAC-IN-85 (Compound 1) is an HDAC inhibitor capable of crossing the blood-brain barrier. It exhibits inhibitory effects on brain tumor cell lines and can induce acetylation, resulting in DNA double-strand breaks and promoting RAD51 ubiquitination, which disrupts the DNA repair process. HDAC-IN-85 is applicable in studies of glioblastoma.

Multi-target kinase inhibitor 4 (Compound 2) is a PI3K/DNA-PK inhibitor and a potent chemosensitizer that enhances the number of DNA double-strand breaks induced by Doxorubicin. It serves as an effective multidrug resistance (MDR) inhibitor, demonstrating inhibitory activity against P-glycoprotein (P-gp) mediated drug efflux. Multi-target kinase inhibitor 4 can be encapsulated in PEG-coated lipid nanoparticles.

NBTIs-IN-7 (compound 276) is an innovative bacterial topoisomerase inhibitor (NBTIs). In the presence of gyrase, NBTIs-IN-7 is capable of inducing both single-strand and double-strand DNA breaks.

CDK9/EZH2-IN-1 is a dual-target inhibitor of CDK9 and EZH2 with IC50 values of 83.9 nM and 108.6 nM, respectively. It induces apoptosis and causes DNA double-strand breaks (DSB). Additionally, CDK9/EZH2-IN-1 inhibits the proliferation of MKN45, MDA-MB-453, and SW620 cancer cells, with respective IC50 values of 136.3 nM, 171.3 nM, and 315.7 nM.

HQY1428 is an orally active CDK12 inhibitor. It impedes DNA replication, causing cell cycle arrest at the G2/M phase in SKOV3 cells, and induces DNA double-strand breaks as well as apoptosis. In the SKOV3 xenograft mouse model, HQY1428 demonstrates antitumor activity. Additionally, when combined with the HER2 inhibitor Lapatinib in the NCI-N87 xenograft mouse model, HQY1428 produces a synergistic therapeutic effect.

7-tert-Butylfascaplysin (7-TB) is a derivative of Fascaplysin, isolated from Fascaplysinopsis sp. It induces replication stress, leading to toxic DNA double-strand breaks and apoptosis-like cell death, exhibiting nanomolar cytotoxicity against cancer cells. Additionally, 7-tert-Butylfascaplysin demonstrates DNA intercalation activity, with an EC50 of 3.2 μM.

EXO1-IN-1 (Compound F684) is a potent and selective inhibitor of exonuclease 1 (EXO1) with an IC50 of 15.7 μM. It inhibits DNA end resection, promotes the accumulation of DNA double-strand breaks, and induces S-phase polyadenylation, thereby disrupting DNA repair pathways in homologous recombination-deficient (HRD) cancer cells. This selectivity effectively targets and kills tumor cells with homologous recombination gene defects, such as BRCA1/2 mutations. EXO1-IN-1 holds promise for researching cancers with homologous recombination deficiencies, including BRCA-related tumors.

ML-20, an analog of Malabaricone C, functions as both an autophagy inhibitor and a radiosensitizer. It suppresses cell proliferation and induces apoptosis (cell death). ML-20 also causes DNA double-strand breaks, loss of mitochondrial membrane potential (MMP), and lysosomal membrane permeabilization (LMP). Due to LMP, it triggers endoplasmic reticulum stress while concurrently inhibiting autophagic flux.