DNA Damage/DNA Repair

Trastuzumab is a humanized monoclonal antibody for patients with invasive breast cancers that overexpress HER2. Trastuzumab has been clinically used to treat HER2 Positive Metastatic Breast Cancer and HER2 Positive Gastric Cancer.

Elimusertib (BAY-1895344) is a potent, highly selective, and orally available ATR inhibitor with an IC50 of 7 nM, demonstrating significant anti-tumor efficacy as a monotherapy and strong combination potential with targeted alpha therapy Radium-223 dichloride.

CAM 833 is an effective orthosteric inhibitor of the BRCA2-RAD51 interaction, inhibiting RAD51 aggregation, enhancing DNA damage-induced apoptosis, increasing 4N cell cycle arrest, and disrupting homologous DNA repair (HDR), and can be used for cancer therapy.

Methoxyamine HCl (Methoxyamine) covalently binds to apurinic/apyrimidinic (AP) DNA damage sites and inhibits base excision repair (BER), which may result in an increase in DNA strand breaks and apoptosis. Methoxyamine is an orally bioavailable small molecule inhibitor with potential adjuvant activity. This agent may potentiate the anti-tumor activity of alkylating agents.

Niraparib (MK-4827) is a PARP inhibitor that selectively targets PARP1 and PARP2 (IC50=3.8/2.1 nM), exhibiting antitumor activity, inhibiting DNA damage repair, and inducing apoptosis.

1-Methyladenine is a DNA alkylation product that undergoes damage reversal through oxidative demethylation for repair purposes.

Tuvusertib (M1774) is an orally available ataxia telangiectasia and Rad3-related (ATR) kinase inhibitor (Ki< 1 µΜ) with selective and potentially antitumor activity.Tuvusertib selectively inhibits ATR activity and blocks downstream phosphorylation of serine/threonine protein kinase checkpoint kinase 1 (CHK1), thereby inhibits DNA damage checkpoint activation, disrupting DNA damage repair and inducing apoptosis in tumor cells.

Emzadirib (RAD51-IN-2) is a potent inhibitor of RAD51, showing potential anticancer activity and useful for studying DNA damage repair.

Amuvatinib hydrochloride (MP470 hydrochloride) is an orally administered multi-targeted tyrosine kinase inhibitor effective against mutant forms of c-Kit, PDGFRα, Flt3, c-Met, and c-Ret, and it suppresses DNA repair by inhibiting the RAD51 protein, contributing to its antineoplastic activity[1][2][3][4].

AB25583 is a potent inhibitor of the Polθ helicase domain (Polθ-hel). It blocks MMEJ repair, leading to DNA damage accumulation and synthetic lethality in BRCA1/2-deficient cancer cells.

KL-50, a selective toxin, effectively targets tumors deficient in the DNA repair protein O6-methylguanine-DNA-methyltransferase (MGMT), which corrects O6-alkylguanine lesions. This compound induces both DNA damage response pathways and cell cycle arrest in MGMT-deficient cells, regardless of mismatch repair (MMR) status. KL-50 shows promise in the study of brain tumors lacking MGMT.

MTH1 activator-1 is an MTH1 activator that enhances endogenous MTH1 activity and significantly reduces 8-oxo-dG levels in cellular DNA. It is useful for investigating the upregulation of oxidative damage repair in nucleotide pools and examining biological effects, as well as for studies aiming to delay or prevent tumorigenesis.

F-ara-EdU is a low-toxicity, highly stable DNA synthesis probe that labels cell proliferation and DNA replication by binding to DNA or RNA in cells. It can also be employed to measure the rate of DNA synthesis within cells and to study the mechanisms of DNA repair and damage.

Octamethylcyclotetrasiloxane promotes the growth of MCF-10A and MCF-10F cells under non-adherent conditions. It induces DNA damage upon prolonged high concentration exposure and inhibits the expression of DNA repair protein BRCA1. Additionally, octamethylcyclotetrasiloxane exhibits inherent estrogenic activity.

USP1-IN-11 (compound 38-P2) is a selective, reversible, and non-competitive inhibitor of USP1 (Ubiquitin-specific protease 1). It activates the DDR (DNA damage repair) pathway, leading to cell cycle arrest and apoptosis, thereby inhibiting cell survival. USP1-IN-11 increases sensitivity to Olaparib in drug-resistant cells and works synergistically with Andrographolide in cancer cells with functional BRCA. In the MDA-MB-436 xenograft model, USP1-IN-11 demonstrates significant dose-dependent antitumor activity.

USP1-IN-11 (compound 38-P2) is a selective, reversible, and non-competitive inhibitor of USP1 (Ubiquitin-specific protease 1). It promotes the activation of the DDR (DNA damage repair) pathway, inducing cell cycle arrest and apoptosis, thereby inhibiting cell viability. USP1-IN-11 increases the sensitivity of cells resistant to Olaparib and shows synergistic effects with Andrographolide in cancer cells with normal BRCA function. In the MDA-MB-436 xenograft model, USP1-IN-11 exhibits a significant dose-dependent antitumor effect.

CW-2 is a PARP1 PROTAC degrader known for its potent antiproliferative effects against MDA-MB-231 cells (IC50 = 0.72 μM) and cisplatin-resistant cells (A549/CDDP: IC50 = 3.52 μM). It exhibits synergistic antitumor activity and enhanced membrane permeability. CW-2 exerts its antitumor effects by inducing DNA damage, disrupting DNA repair, and triggering mitochondrial-dependent apoptosis (apoptosis).

CDK12-IN-8 (Compound Cpd143) is an orally active, highly selective inhibitor of cyclin-dependent kinase 12 (CDK12). It blocks the phosphorylation of serine 2 in the C-terminal domain (CTD) of RNA polymerase II, thereby interfering with gene transcription elongation and DNA damage repair pathways. CDK12-IN-8 holds potential for research in cancers with high CDK12 expression, such as small cell lung cancer and triple-negative breast cancer.

Z57346765 hydrochloride is an inhibitor of phosphoglycerate kinase 1 (PGK1) that binds to the ADP binding site, with a K\(_D\) value of 2.09 × 10⁻⁵ M, thereby reducing the metabolic enzyme activity of PGK1, glucose consumption, and lactate production. Additionally, it inhibits DNA replication, impairs DNA damage repair, and induces cell cycle arrest in renal clear cell carcinoma (KIRC) cells.

PROTACPARP1 degrader-1 (Compound CN0) serves as a PROTAC degrader of PARP1. It activates the cGAS/STING immune pathway, ultimately enhancing T cell-mediated tumor cell killing. PROTACPARP1 degrader-1 inhibits DNA damage repair, leading to the efficient accumulation of cytoplasmic DNA fragments.

3-Methylguanine is a DNA damage product resulting from alkylation. It exhibits cytotoxicity by inhibiting DNA replication, leading to cell death. 3-Methylguanine is utilized to study the mechanisms of DNA damage by alkylating agents and the pathways involved in its repair.

ADP-ribose/PARP-IN-1 (Compound Ex.16) is a conjugated compound composed of a disease-targeting segment, a PARP inhibitor section, a cleavable linker, and a chelating agent. It targets specific sites via its disease-targeting part, delivering the PARP inhibitor selectively to tumor cells. Under suitable conditions, the cleavable linker releases the PARP inhibitor to hinder DNA damage repair by inhibiting PARP, while the chelating agent transports a radionuclide for cytotoxic action. This compound is applicable in prostate cancer research.

NU-PRO-1 is a covalent telomerase reverse transcriptase (TERT) PROTAC degrader. While NU-PRO-1 on its own does not cause DNA damage, it significantly delays DNA repair following radiation exposure.

Etoposide Phosphate is a selective and orally active topoisomerase II inhibitor and anticancer chemotherapy drug that inhibits cancer cell growth and induces apoptosis through DNA damage, the p53 pathway, and G2/M phase arrest of the cell cycle.