COH29 (RNR Inhibitor COH29) is an orally available, aromatically substituted thiazole and inhibitor of the human ribonucleotide reductase (RNR), with potential antineoplastic activity. Upon oral administration, the RNR inhibitor COH29 binds to the ligand-binding pocket of the RNR M2 subunit (hRRM2) near the C-terminal tail. Inhibition of RNR activity decreases the pool of deoxyribonucleotide triphosphates available for DNA synthesis. The resulting decrease in DNA synthesis causes cell cycle arrest and growth inhibition. In addition, this agent may inhibit the nuclear enzyme poly (ADP-ribose) polymerase (PARP) 1, which prevents the repair of damaged DNA and causes both the accumulation of single and double strand DNA breaks and the induction of apoptosis.

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.

UNC3474, a small molecule ligand, selectively interacts with the aromatic methyl-lysine binding cage of the tumor protein 53BP1 Tudor domain (TT), exhibiting a dissociation constant (Kd) of 1.0±0.3 μM. It impedes 53BP1's recruitment to DNA double-strand breaks (DSBs), maintaining the protein's autoinhibited state within cells [1].

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.

Amsacrine Isothionate is an aminoacridine derivative with potential antineoplastic activity. Although its mechanism of action is incompletely defined, amsacrine may intercalate into DNA and inhibit topoisomerase II, resulting in DNA double-strand breaks, arrest of the S/G2 phase of the cell cycle, and cell death.

PARP1-IN-12, a potent inhibitor of PARP1, demonstrates an IC50 value of 2.99 nM. It exhibits antiproliferative effects, induces apoptosis, and causes cell cycle arrest in the G2/M phase. Additionally, PARP1-IN-12 induces DNA double-strand breaks (DSBs) in BRCA-deficient cells.

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.

Etoposide phosphate is a phosphate salt of Etoposide, which binds to the enzyme topoisomerase II, then induces double-strand DNA breaks and inhibits DNA repair, leading to decreased DNA synthesis and tumor cell proliferation.

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.

p53 Activator 2 (compound 10ah) intercalates into DNA, causing significant DNA double-strand breaks and upregulates the expression of p53, p-p53, CDK4, and p21, leading to cell cycle arrest at the G2/M phase. It induces apoptosis, significantly reduces the expression of anti-apoptosis proteins Bcl-2, Bcl-xL, and cyclin B1 levels, and exhibits anti-proliferative activity against MGC-803 cells with an IC50 of 1.73 μM. Furthermore, p53 Activator 2 demonstrates potent anticancer effectiveness in MGC-803 xenograft tumor models [1].

Cu(II)-Elesclomol, a Cu 2+ complex of Elesclomol, exhibits anticancer activity by inducing apoptosis, causing a G1 cell cycle block, and inducing DNA double strand breaks in K562 cells. Additionally, it weakly inhibits DNA topoisomerase I [1].

DiPT-4, a dual TOP1/PARP1 inhibitor, effectively induces DNA double-strand breaks (DSBs), cell cycle arrest, and apoptosis in cancer cells, with potential to circumvent drug resistance [1].

NSC 617145 (NSC617145) is an inhibitor of WRN helicase that inhibits the ATPase, but not exonuclease, activity of WRN helicase in a concentration-dependent manner.

Amonafide L-malate is the malate salt of amonafide, an imide derivative of naphthalic acid, with potential antineoplastic activity. Amonafide intercalates into DNA and inhibits topoisomerase II, resulting in DNA double-strand breaks (DSB) and inhibition of DNA replication and RNA synthesis.

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

Topoisomerase II inhibitor 6 (Compound 5) is a tryptanthrin derivative. Topoisomerase II inhibitor 6 is a potent and selective topoisomerase II inhibitor. Topoisomerase II inhibitor 6 blocks the CCRF-CEM cell cycle in the G2 phase and induces DNA double-strand breaks (DSB). Topoisomerase II inhibitor 6 exhibits antiproliferative activity on different tumor cell lines. Topoisomerase II inhibitor 6 has the potential for the research of cancer diseases [1].

Cylindrospermopsin, a tricyclic uracil derivative, is a cyanobacterial toxin that was first discovered in an algal bloom contaminating a local drinking supply on Palm Island in Queensland, Australia after an outbreak of a mysterious disease. Cylindrospermopsin targets protein and glutathione synthesis in hepatocytes (IC50s = 1.3 and 2.4 µM, respectively), leading to cell death. [1] It has been shown to inhibit the activity of the uridine monophosphate synthase complex with a Ki value of 10 µM.[2] Cylindrospermopsin is genotoxic, inducing DNA damage as evidenced by double strand breaks and reducing cell viability in HepG2 cells at 0.1-0.5 µg/ml.[3]

5-BrdUTP sodium salt is a TdT substrate that can be used to label the DNA double-strand breaks.

Selenocystine, a broad-spectrum anticancer agent, effectively induces DNA damage, notably DNA double-strand breaks (DSBs), in HepG2 cells, showcasing significant potential as a therapeutic or adjuvant agent in targeting DNA repair mechanisms for cancer treatment [1].

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 DNA double-strand breaks. It induces apoptosis in cancer cells via the mitochondrial pathway [1].

PARP1-IN-15 (Compound 6) is a PARP1 inhibitor that also inhibits tankyrase (TNKS) and promotes DNA double-strand breaks, leading to tumor cell apoptosis. It exhibits anti-cancer activity in triple-negative breast cancer (TNBC) cells and patient-derived organoids, making it useful for TNBC research, including cases with or without BRCA1 mutations [1].

Amsacrine gluconate is an aminoacridine derivative with potential antineoplastic activity. Although its mechanism of action is incompletely defined, amsacrine may intercalate into DNA and inhibit topoisomerase II, resulting in DNA double-strand breaks, arrest of the S/G2 phase of the cell cycle, and cell death.

Amsacrine lactate is an aminoacridine derivative with potential antineoplastic activity. Although its mechanism of action is incompletely defined, amsacrine may intercalate into DNA and inhibit topoisomerase II, resulting in DNA double-strand breaks, arrest of the S/G2 phase of the cell cycle, and cell death.