As a leading supplier for ADC cytotoxin discovery and manufacture, BOC Sciences provides a wide range of specific products that induce DNA damage to support your research. The primarily cytotoxicity of DNA damage is manifested as inhibitory on vital cellular processes, such as transcription and replication. The anticancer activities of various chemotherapeutic agents rely on the cytotoxic consequences of DNA damage. Some tumor cells may acquire DNA repair defects during carcinogenesis because the loss of DNA surveillance contributes to hypermutable phenotype and drives early tumor development. Thus, tumor-specific defects in DDR present a unique opportunity for cancer-specific therapies. However, most cancer cells would be expected to have proficient DNA repair pathways. Therefore, therapeutic targeting specific components of DNA repair pathways in cancer cells require treatment efficacy enhancement.
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As a biological macromolecule, DNA (deoxyribonucleic acid) composed genetic instructions to guide biological development and life functions. The main function of DNA is information storage, which can be compared to a “blueprint” or “recipe”. DNA damages apply permenant effect to DNA nucleotide sequence which occurs during the replication process and modifies genetic characteristics. DNA damge not only disrupts the nucleic acid architecture, but also leads to the killing of cancer cells through apoptosis. Biologically, various mutagens could induce DNA damages, including oxidants, alkylating agents, and high-frequency electromagnetic radiation including ultraviolet rays and X-rays. The most important DNA damage response pathways components were seen as potential cancer therapeutic targets, and numerous chemical inhibitors were designed and synthesized to target this pathway's protein. Proteins and pathways involved in with DNA damage response were catagoried into four functional groups: DNA repair, DNA repair accessory functions, DNA damage signaling, and cell survival. Novel drug development targeting DNA damage response is an active field of research and considerable interest to pharmaceutical companies.
Anal. Chem. 2011, 83, 9, 3248–3251.
DNA-binding cytotoxins exert cytotoxic effects by binding to DNA in the double helix groove. Calicheamicins, Duocarmycins, Camptothecins and Pyrrolobenzodiazepines (PBD) represent these cytotoxic drugs, all of which exhibit potent activity. These small molecules tend to bind to the minor grooves of DNA and promote alkylation, cleavage, or cross-linking strands. N-acetyl-γ-calicheamicin is commonly used as a DNA damaging agent in ADC structure for Gemtuzumabozogamicin and Inotuzumabozogamicin. It is worth noting that, due to strong hydrophobicity of Calicheamicin, each monoclonal antibody can only couple a few molecules in order to avoid aggregation of proteins.