Topotecan Hydrochloride is the water-soluble hydrochloride salt preparation of Topotecan, a potent inhibitor of topoisomerase 1, and an apoptosis inducer, producing proapoptotic and antiproliferative effects. Topotecan is a semisynthetic derivative of the natural product alkaloid camptothecin. It is described to stabilize topoisomerase I/DNA cleavable complexes and promote rapid apoptotic cell death in radiation-resistant human B-lineage acute lymphoblastic leukemia cells.
CAT No: 10-101-124
CAS No:123948-87-8 (net), 119413-54-6 (hydrochloride)
Synonyms/Alias:TPT; SKF-104864A; SKFS-104864-A; 9-[(Dimethylamino)methyl]-10-hydroxy-(20S)-camptothecin · HCl; (S)-10-Dimethylaminomethyl-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2b]quinoline-3,14(4H,12H)-dione · HCl; (20S)-10-Dimethylaminomethyl-4-ethyl
Topotecan Hydrochloride is a synthetic derivative of camptothecin, classified as a topoisomerase I inhibitor, and is widely recognized for its role in modulating DNA topology during replication and transcription. As a potent small-molecule compound, it has become an essential tool in biochemical research focused on DNA damage, repair mechanisms, and cell cycle regulation. Its unique ability to stabilize the cleavable complex between DNA and topoisomerase I makes it particularly valuable for mechanistic studies in molecular biology, cellular biochemistry, and drug development. The compound's distinct chemical structure and mode of action have positioned it as a reference agent in the exploration of topoisomerase-mediated processes and cellular responses to genotoxic stress.
DNA Damage and Repair Research: Topoisomerase I inhibitors such as topotecan hydrochloride are integral to investigations of DNA strand breakage and repair pathways. By preventing the religation of single-strand breaks introduced by topoisomerase I, topotecan induces persistent DNA lesions, which can be quantitatively and qualitatively analyzed to elucidate the kinetics and fidelity of DNA repair mechanisms. Researchers utilize this compound to probe the cellular machinery involved in homologous recombination, non-homologous end joining, and other repair pathways, thereby gaining insights into genome stability and the cellular response to genotoxic insults.
Cell Cycle and Apoptosis Studies: The capacity of topotecan hydrochloride to disrupt normal DNA replication provides a robust model for studying cell cycle arrest and apoptosis induction. In vitro experiments frequently employ this agent to synchronize cell populations, monitor checkpoint activation, and assess downstream signaling events triggered by DNA damage. Its use facilitates the dissection of molecular cascades governing cell fate decisions, enabling researchers to map critical nodes within the network of cell cycle regulators and apoptotic effectors.
Genotoxicity and Mutagenesis Assays: The compound's well-characterized mechanism of inducing DNA breaks makes it a reliable positive control in genotoxicity testing and mutagenesis assays. Laboratories employ topoisomerase I inhibitors in standardized protocols such as comet assays, micronucleus tests, and chromosome aberration analyses to validate assay sensitivity and to benchmark the DNA-damaging potential of novel compounds. These applications are vital for toxicological screening, chemical risk assessment, and the development of safer chemicals in pharmaceutical and industrial contexts.
Mechanistic Drug Interaction Studies: Topotecan hydrochloride is frequently used to investigate drug-drug interactions and synergistic effects in combination therapy research. Its defined molecular target and predictable cellular outcomes allow researchers to explore the interplay between DNA-damaging agents and other modulators of cell survival, such as checkpoint inhibitors, DNA repair inhibitors, or epigenetic modifiers. Such studies support the rational design of combination regimens and contribute to a deeper understanding of compound synergy, antagonism, or potentiation at the molecular level.
Biochemical Target Validation: In the context of target engagement and validation, topoisomerase I inhibitors serve as benchmark molecules for confirming the functional relevance of topoisomerase I in diverse biological systems. By employing topotecan hydrochloride in enzymatic assays, cell-based models, or genetic manipulation studies, researchers can directly assess the consequences of topoisomerase I inhibition, verify the specificity of novel inhibitors, and delineate off-target effects. This application is fundamental to the advancement of next-generation topoisomerase-targeting agents and the refinement of screening platforms for drug discovery.
The stability and compatibility of topotecan hydrochloride with common infusion solutions and containers were studied. During this study, the leaching of diethylhexyl phthalate (DEHP), a major plasticizer of some polyvinyl chloride (PVC) materials was also investigated. A formulation of topotecan hydrochloride was added to 50 ml PVC infusion bags, polyolefin infusion bags and 150 ml glass bottles containing either 5% dextrose injection or 0.9% sodium chloride injection at an initial nominal topotecan concentration of 0.05 mg ml-1. Additionally, the topotecan hydrochloride formulation was added to 50 ml PVC infusion bags containing either 5% dextrose injection or 0.9% sodium chloride injection at an initial nominal topotecan concentration of 0.025 mg ml-1.
Craig, S. B., Bhatt, U. H., & Patel, K. (1997). Stability and compatibility of topotecan hydrochloride for injection with common infusion solutions and containers. Journal of pharmaceutical and biomedical analysis, 16(2), 199-205.
Ovarian cancer is the most common gynaecological cancer, with an annual incidence of 21.9 per 100,000 women in England and 26.7 per 100,000 in Wales (2000 figures). The prognosis is generally poor, owing to the advanced stage of disease at detection in most cases, and the UK 5-year survival rate is only around 30%. The current guidance issued by the National Institute for Health and Clinical Excellence is that first-line chemotherapy should include either paclitaxel in combination with a platinum-based chemotherapy regimen, or a platinum-based regimen alone (carboplatin or cisplatin). As the majority of patients ultimately relapse and require treatment with second-line therapy, the guidance is that patients who have received recommended first-line therapy should not be treated with the same agents. Pegylated liposomal doxorubicin hydrocholoride (PLDH), topotecan and paclitaxel may therefore be considered alongside other drugs licensed for second-line therapy in advanced ovarian cancer. Participants who had not received paclitaxel as a component of first-line therapy may receive it as second-line.
Main, C., Bojke, L., Griffin, S., Norman, G., Barbieri, M., Mather, L., ... & Riemsma, R. (2006). Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for second-line or subsequent treatment of advanced ovarian cancer: a systematic review and economic evaluation.
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