(E)-Triapine

Triapine (CAS No.: 200933-27-3) is a synthetic small-molecule research tool compound of the α-N-heteroaryl thiosemicarbazone family, also known as 3-AP, commonly found as the E-configured isomer, and is mainly used in biomedical research and the early stages of drug discovery, particularly for elucidating fundamental processes such as ribonucleotide metabolism, replication stress, and DNA damage response in oncology-oriented experimental systems; as a potent ribonucleotide reductase (RNR) inhibitor, it targets the iron-dependent tyrosyl radical site in the class I RNR small subunit, inhibiting the activity of RRM2 and the p53R2 variant through iron chelation and redox-mediated radical quenching, thereby blocking the conversion of ribonucleotides to deoxyribonucleotides, rapidly reducing intracellular dNTP pools, and limiting DNA synthesis and S-phase progression; in vitro studies show that it has significant antiproliferative activity in various human tumor cell lines, with potency typically in the submicromolar to low micromolar range; in applications, Triapine is commonly used for short-term exposure in cell culture systems to induce dNTP starvation and S-phase arrest, as a reference inhibitor in enzymology experiments, or as a chemical probe under DNA-damaging conditions or in combination with ionizing radiation to characterize interactions within replication-repair networks, and is also used in research models including L1210 leukemia to investigate RNR dependence and control of DNA synthesis; additionally, it is widely used in drug discovery-related research scenarios such as target validation, pathway mapping, and combination strategy screening, with the treatment concentration or exposure level used in experiments typically depending on the specific experimental design and research objectives.