• Topotecan inhibits topoisomerase I, inhibiting DNA replication. (medscape.com)
  • Contrary to other anticancer targets, topoisomerase I (TOP1) is targeted by only one chemical class of FDA-approved drugs: topotecan and irinotecan, the derivatives of the plant alkaloid, camptothecin. (usuhs.edu)
  • Although topotecan (TPT), a topoisomerase1 inhibitor, is a first- and second-line drug for lung and colon cancers, the development of drug resistance and toxicity still remain as a major obstacle to chemotherapeutic success. (uaeu.ac.ae)
  • The research, published in the Proceedings of the National Academy of Sciences , shows how the common chemotherapy drug topotecan can drastically suppress the expression of Topoisomerase-1, a gene that triggers the creation of proteins essential for normal brain function. (sciencedaily.com)
  • This discovery led them to investigate how topotecan affects the specific topoisomerase enzymes in cancer cells and in neurons. (sciencedaily.com)
  • In the PNAS paper, the researchers describe how topotecan hits its intended target -- the topoisomerase proteins that are integral for cell division, a hallmark of cancer cells. (sciencedaily.com)
  • These experiments used only topotecan, but there's an entire class of topoisomerase inhibitors. (sciencedaily.com)
  • Studies searching for antibiotic and anticancer agents in the mid to late 20th century have illuminated the existence of numerous unique families of both TopI and TopII inhibitors, with the 1960s alone resulting in the discovery of the camptothecin, anthracycline and epipodophyllotoxin classes. (wikipedia.org)
  • Topoisomerase inhibitor classes have been derived from a wide variety of disparate sources, with some being natural products first extracted from plants (camptothecin, etoposide) or bacterial samples (doxorubicin, indolocarbazole), while others possess purely synthetic, and often accidental, origins (quinolone, indenoisoquinoline). (wikipedia.org)
  • Currently, topoisomerase inhibitors hold a prominent place among antibiotics and anticancer drugs in active medical use, as inhibitors like doxorubicin (anthracycline, TopII inhibitor), etoposide (TopII inhibitor), ciprofloxaxin (fluoroquinolone, TopII inhibitor), and irinotecan (camptothecin derivative, TopI inhibitor) were all included in the 2019 WHO Model List for Essential Medicines. (wikipedia.org)
  • Camptothecin-derived TopI inhibitors function by forming a ternary complex with TopI-DNA and are able to stack between the base pairs that flank the cleavage site due to their planar structure. (wikipedia.org)
  • Camptothecin analogs as potent inhibitors of topoisomerase I . (U.S. Patent No. 5106742 ). (rti.org)
  • The camptothecin analogs are effective inhibitors of topoisomerase I and show anti-leukemic and anti-tumor activity. (rti.org)
  • Zymeworks Topoisomerase-1 inhibitor technology uses a novel fit-for-purpose camptothecin payload with moderate potency and strong bystander activity in conjunction with a traceless, plasma-stable, cleavable peptide linker. (zymeworks.com)
  • We have shown that colorectal cancer cell lines defective in DNA MMR exhibit an increased sensitivity to both camptothecin, a topoisomerase I inhibitor, and etoposide, a topoisomerase II inhibitor. (aacrjournals.org)
  • Genz-644282 is a non-camptothecin inhibitor of topoisomerase I with potential antineoplastic activity. (adooq.com)
  • Drugs called mitotic inhibitors stop cancer cells from making more copies of themselves. (webmd.com)
  • Topoisomerase inhibitors have been used as important experimental tools that have contributed to the discovery of some topoisomerases, as the quinolone nalidixic acid helped elucidate the bacterial TopII proteins it binds to. (wikipedia.org)
  • Occupational exposure limits with proteins such as topoisomerase inhibitors, and mitotic and meiotic spindle poisons. (cdc.gov)
  • Repair of topoisomerase 1 (TOP1) DNA protein crosslinks (DPC) limits the efficacy of the TOP1 inhibitor irinotecan in cancer therapy. (nature.com)
  • Here, the authors identify pevonedistat, NEDD8 inhibitor, as synergistic with irinotecan by blocking neddylation-activated ubiquitin/proteasomal degradation of TOP1-DPC. (nature.com)
  • Krop noted that the drug is 10 times more potent than topoisomerase I inhibitors such as irinotecan, one of the more typically-used drugs in this class. (medpagetoday.com)
  • Knowledge of the first topoisomerase inhibitors, and their medical potential as anticancer drugs and antibiotics, predates the discovery of the first topoisomerase (Escherichia. (wikipedia.org)
  • Bortezomib is the first drug approved in the group of anticancer agents known as proteasome inhibitors. (medscape.com)
  • Dr. Yalowich's lab focuses on the mechanisms of action and resistance to DNA topoisomerase II (topo II)-targeted agents, such as the anticancer agent etoposide (VP-16). (osu.edu)
  • In this study, treatment of EMT6 mouse mammary tumor cells with hypoxia or the chemical stress agents brefeldin A (BFA) or okadaic acid (OA) causes the development of resistance to the topoisomerase II inhibitor etoposide. (aspetjournals.org)
  • CRISPR/Cas9 Genome Editing of the Human Topoisomerase II Intron 19 5' Splice Site Circumvents Etoposide Resistance in Human Leukemia K562 Cells. (osu.edu)
  • hsa-miR-9-3p and hsa-miR-9-5p as Post-Transcriptional Modulators of DNA Topoisomerase II in Human Leukemia K562 Cells with Acquired Resistance to Etoposide. (osu.edu)
  • Biological Activity: Topoisomerase I/II inhibitor 3 (compound 7) is a potent topoisomerase I (Topo I) and II (Topo II) dual inhibitor. (epigenetics-modulation-frontier.com)
  • RHPS4 is a potent inhibitor of Telomerase at submicromolar. (adooq.com)
  • Catabolism of the ADC following target engagement, internalization, and lysosomal trafficking releases the topoisomerase inhibitor payload ZD06519. (zymeworks.com)
  • Trastuzumab deruxtecan is an antibody drug conjugate with three key components: an anti-HER2 monoclonal antibody with the same amino acid as trastuzumab, a topoisomerase I inhibitor payload, and a tetra-peptide-based cleavable linker. (medpagetoday.com)
  • The ADCs sacituzumab govitecan (Trodelvy) and trastuzumab deruxtecan (Enhertu), for instance, both incorporate a topoisomerase inhibitor as their toxic payload. (medscape.com)
  • Similarly, trastuzumab emtansine (Kadcyla), enfortumab vedotin (Padcev), mirvetuximab soravtansine (Elahere), and tisotumab vedotin (Tivdak), which have a microtubule inhibitor as the payload, come with similar toxicities to the microtubule-inhibiting drugs. (medscape.com)
  • SN-38 binds to and stabilizes the topoisomerase I-DNA complex and prevents the relegation of DNA after it has been cleaved by topoisomerase I, inhibiting DNA replication. (medscape.com)
  • Topoisomerases are nuclear enzymes that modify the topological state of DNA and participate in fundamental metabolic processes such as replication, transcription, repair, recombination, and chromosome segregation (1) . (aacrjournals.org)
  • Topoisomerases are essential nuclear enzymes with a multiplicity of cellular functions involving DNA replication, RNA transcription, mitosis, and chromosome condensation. (annals.edu.sg)
  • Another type of medicine, called topoisomerase inhibitors, also attacks enzymes that help cancer cells divide and grow. (webmd.com)
  • Pretreatment with the proteasome inhibitor carbobenzyoxyl-leucinyl-leucinyl-leucinal inhibits stress-induced NF-κB activation and reverses BFA-induced drug resistance. (aspetjournals.org)
  • Reversible proteasome inhibitor. (medscape.com)
  • detailed the discovery of the bacterial TopII DNA gyrase and discussed its inhibition when introduced to coumarin and quinolone class inhibitors, sparking greater interest in topoisomerase-targeting antibiotic and antitumor agents. (wikipedia.org)
  • Oral Pharmacokinetics and Efficacy of BWC0977, a Novel Bacterial Topoisomerase Inhibitor. (asm.org)
  • Dioxane-Linked Amide Derivatives as Novel Bacterial Topoisomerase Inhibitors against Gram-Positive Staphylococcus aureus. (osu.edu)
  • Novel bacterial topoisomerase inhibitors derived from isomannide. (osu.edu)
  • Gepotidacin (GlaxoSmithKline) is another bacterial topoisomerase II inhibitor with good in vitro activity against a wide range of drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus , extended-spectrum beta-lactamase-producing Enterobacteriaceae , and N gonorrhoeae . (medscape.com)
  • The indenoisoquinolines LMP400, LMP744, and LMP776 are novel noncamptothecin TOP1 inhibitors in clinical trial, which overcome the limitations of camptothecins. (usuhs.edu)
  • Some topoisomerase inhibitors prevent topoisomerases from performing DNA strand breaks while others, deemed topoisomerase poisons, associate with topoisomerase-DNA complexes and prevent the re-ligation step of the topoisomerase mechanism. (wikipedia.org)
  • TMPyP4 tosylate (TMP 1363) is a telomerase inhibitor with antitumor effects in osteosarcoma cell lines. (adooq.com)
  • VEGF inhibitors directly bind to the VEGF protein to disrupt angiogenesis. (medscape.com)
  • Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases, which are broken into two broad subtypes: type I topoisomerases (TopI) and type II topoisomerases (TopII). (wikipedia.org)
  • Treatment with TopI inhibitors stabilizes the intermediate cleavable complex, preventing DNA re-ligation, and inducing lethal DNA strand breaks. (wikipedia.org)
  • In cancer cells, however, these checkpoints are typically inactivated, making them selectively sensitive to TopI inhibitors. (wikipedia.org)
  • Exploring Potential MCR-1 Inhibitors: Restoring In Vitro Polymyxin Activity in MCR-1-Producing Enterobacteriales. (asm.org)
  • Topoisomerase inhibitors inhibit cell growth and proliferation. (medscape.com)
  • Topoisomerase plays important roles in cellular reproduction and DNA organization, as they mediate the cleavage of single and double stranded DNA to relax supercoils, untangle catenanes, and condense chromosomes in eukaryotic cells. (wikipedia.org)
  • It was identified that the nuclear division cycle 80, cyclin B2 and topoisomerase 2‑α may serve important roles in adrenocortical tumor development. (cancerindex.org)
  • It is described as an angiogenesis inhibitor and a phytoestrogen . (wikipedia.org)
  • Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases . (github.io)
  • Resistance to fluoroquinolones in S . pneu- with MIC 4-8 µg/mL) was caused by a reserpine-sensitive moniae can be acquired by point mutations, intraspecific efflux phenotype (n = 4) or single topoisomerase IV ( parC [n = 24] or parE [n = 1]) changes. (cdc.gov)
  • Topoisomerase inhibitors have gained interest as therapeutics against infectious and cancerous cells. (topoisomerasesignaling.com)
  • Zoliflodacin (Entasis Therapeutics), a first-in-class spiropyrimidinetrione topoisomerase II inhibitor with activity against several pathogens, including N gonorrhoeae and C trachomatis . (medscape.com)
  • Biological evaluation, docking studies, and in silico ADME prediction of some pyrimidine and pyridine derivatives as potential EGFR WT and EGFR T790M inhibitors. (bvsalud.org)
  • Sensitivity to these drugs cannot be predicted by measuring endogenous levels of topoisomerase I and II. (aacrjournals.org)
  • Intercalating drugs block the reconnection step, freezing the topoisomerase after it has broken the DNA. (github.io)
  • It acts throughout the entire cell cycle and by direct intercalating into DNA triggers DNA breakage by topoisomerase II, causing subsequent cytocydal activity. (medscape.com)
  • Costunolide is an Inhibitor of human telomerase activity (IC50 = 65 μM in MCF-7 breast cancer cells). (adooq.com)
  • Topoisomerase inhibitors influence these essential cellular processes. (wikipedia.org)
  • Cell Cycle inhibitor Sleep disturbance was classified into four sleep complaints: difficulty initiating AZD8055 supplier sleep, difficulty maintaining sleep, early-morning awakening, and non-restorative sleep. (topoisomerasesignaling.com)
  • Effect of safranal on the response of cancer cells to topoisomerase I inhibitors: Does sequence matter? (uaeu.ac.ae)