Topoisomerases can manage DNA's topological state in the nuclear to facilitate the replication, recombination, transcription and repair of DNA by separating the two strands of the helix temporarily. There are 2 types of DNA topoisomerases which are type I topoisomerase and type II topoisomerase. [show the full text]
Topoisomerase Inhibiteurs (Topoisomerase Inhibitors)
Autre DNA Damage/DNA Repair Inhibiteurs
| N° Cat. | Nom du produit | Information | Citations d'utilisation du produit | Validations de produits |
|---|---|---|---|---|
| E2516 | Doxorubicin | L'Adriamycine (Doxorubicin, Hydroxydaunorubicin), un antibiotique anthracycline cytotoxique, est un agent de chimiothérapie anticancéreuse, qui inhibe la topoisomerase II avec une IC50 de 2,67 μM, arrêtant ainsi la réplication de l'ADN et induisant l'apoptose. |
|
|
| S1198 | Irinotecan (CPT-11) | Irinotecan est un inhibiteur de la topoisomérase I pour les cellules LoVo et HT-29 avec des IC50 de 15,8 μM et 5,17 μM, respectivement. |
|
|
| S1288 | Camptothecin (CPT) | Camptothecin (CPT) est un inhibiteur spécifique de l'ADN topoisomerase I (Topo I) avec une IC50 de 0,68 μM dans un essai sans cellule. Camptothecin induit l'apoptosis dans les cellules cancéreuses via les voies mitochondriales médiées par le microRNA-125b. Phase 2. |
|
|
| S1208 | Doxorubicin (Adriamycin) Hydrochloride | Doxorubicin (DOX) HCl est un agent antibiotique qui inhibe la DNA topoisomerase II humaine avec un IC50 de 2,67 μM. La Doxorubicin réduit la phosphorylation basale de l'AMPK. La Doxorubicin est utilisée dans le traitement concomitant des patients infectés par le HIV mais s'avère être à haut risque de réactivation du VHB.Ce produit peut précipiter lorsqu'il est dissous dans une solution de PBS. Il est recommandé de préparer la solution mère dans de l'eau pure et de la diluer avec de l'eau pure ou une solution saline pour obtenir la solution de travail.Doxorubicin (Adriamycin) HCl peut être utilisé pour induire des modèles animaux de maladie rénale. |
|
|
| S1225 | Etoposide | Etoposide est un dérivé semi-synthétique de la podophyllotoxine, qui inhibe la synthèse de l'ADN via l'activité inhibitrice de la topoisomerase II, ce qui augmente le clivage double brin et simple brin de l'ADN et inhibe réversiblement la réparation par liaison à la topoisomerase II. Etoposide induit l'autophagy, la mitophagy et l'apoptosis. |
|
|
| S2492 | Novobiocin Sodium (Cathomycin, Albamycin) | Le Novobiocin Sodium (NSC 2382, Albamycin, Cathomycin) est un antibiotique aminocoumarine qui cible la DNA gyrase (TopoIV) bactérienne, utilisé pour traiter les bactéries gram-positives sensibles. |
|
|
| S4908 | SN-38 | SN-38 (NK012) est un métabolite actif du CPT-11, il inhibe la DNA topoisomerase I, la synthèse d'ADN et provoque de fréquentes cassures simple brin de l'ADN. SN-38 induit l'autophagie. |
|
|
| S2217 | Irinotecan Hydrochloride Trihydrate | Irinotecan HCl Trihydrate est un chlorhydrate trihydraté d'Irinotecan (Camptosar, Campto, CPT-11) qui est un inhibiteur de la Topoisomerase I avec une IC50 de 15,8 et 5,17 μM pour les cellules LoVo et les cellules HT-29, respectivement. |
|
|
| S3035 | Daunorubicin Hydrochloride (Daunomycin) | Daunorubicin HCl inhibe à la fois la synthèse de l'ADN et de l'ARN et inhibe la synthèse de l'ADN avec un Ki de 0,02 μM dans un essai sans cellules. La Daunorubicin est un inhibiteur de la topoisomerase II qui induit l'apoptosis.Le Daunorubicin (RP 13057) HCl peut être utilisé pour induire des modèles animaux de maladie rénale. |
|
|
| S1231 | Topotecan HCl | Topotecan HCl est un inhibiteur de la topoisomérase I pour les cellules MCF-7 Luc et les cellules DU-145 Luc avec des IC50 de 13 nM et 2 nM dans des tests sans cellule, respectivement. Ce composé induit l'autophagy et l'apoptosis. |
|
|
DNA topoisomerases are nuclear enzymes that play a critical role in DNA transcription and replication events for the efficient creation and compaction of two identical genomes in two daughter cells. There are at least five different topoisomerase that have been found in higher eukaryotes that can be grouped into two categories: (1) type I family, includes topoisomerases I, IIIα, IIIβ, and (2) type II family, includes topoisomerases IIα and IIβ.[1][2]
Type I enzymes, which do not require ATP, cleave one DNA strand at a time to achieve DNA strand relaxation. More specifically, among type I family constituents, topoisomerase I-mediated DNA strand scission involves a nucleophilic attack by the active site tyrosine OH group on the DNA phosphodiester bond at the site of cleavage. Such an attack results in the breakage of the DNA phosphodiester backbone and the creation of a phosphotyrosine bond between the enzyme and DNA. This covalent binary complex DNA-topoisomerase I, the so-called cleavable complex, is typically only an intermediate. Relaxation via passage (swivel movement) of the broken DNA strand around the unbroken strand is followed by reformation of the phosphodiester backbone as a result of relegation, with concomitant release of topoisomerase I and enzyme turnover.[1][2]
In contrast, type II enzymes which are typically ATP-dependent are able to perform double strand cuts that relieve superhelical twists, intramolecular DNA knots, and intermolecular tangles for chromosomal segregation to produce a DNA-linked protein gate through which another intact duplex can pass. It should be emphasized that the enzyme shows strong preference for supercoiled DNA versus relaxed molecules. More specifically, with topoisomerase II enzymes it is observed that DNA cleavage occurs at preferred sequences within its recognition/binding sites, but there is not clear specificity.[1][2]
In either case, both types of topoisomerases cleave DNA at the phosphodiester backbone by nucleophilic attack from a catalytic tyrosine residue which becomes linked to the phosphate end (P-Y) of the DNA break. The reactions of both types of topoisomerases are highly reversible and leave the DNA sequence unchanged following topoisomerization.[1][2]
While both topoisomerases can relax supercoiled DNA, only topoisomerase II can decatenate DNA molecules. Interestingly, throughout the cell cycle topoisomerase I and topoisomerase IIβ do not change in concentration, meanwhile topoisomerase IIα protein level are noted to fluctuate in relation to the proliferative stage and cell cycle position. In particular, topoisomerase IIα mRNA peak in late S and G2/M several-fold over (typically more than 10 times) the amount observed in G1 cells. The high levels of topoisomerase IIα during the final stages of DNA replication is intended to assist with chromosome untangling, condensation and mitotic segregation events. Consequently, cancerous cells are noted to have high topoisomerase IIα activity, and these findings have prompted researchers to develop new anti-cancer agents that specifically target to poisomerase II.[1][2]
In general, topoisomerase I or topoisomerase II-directed anti-cancer agents are able to interfere with at least one step of the catalytic cycle of the enzyme. Among the topoisomerase I inhibitor class of compounds, Camptothecin (CPT) and its derivatives – a pentacyclic alkaloid formerly isolated as a natural extract from the Chinese tree Camptoteca acuminate – are effective at selectively targeting topoisomerase I by trapping its catalytic intermediate during the topoisomerase I-DNA reaction. Agents that effectively target topoisomerase II include the Anthracyclines (i.e. Adriamycin and Daunorubicin, 9 and 10), Epipodophyllotoxins (i.e. Etoposide and Teniposide 11 and 12), Antracendedione (i.e. Mitoxantrone, 13) and Aminoacrideines (i.e. m-AMSA). The compounds are successful at stabilizing the short-lived covalent complexes between topoisomerase II and DNA. The anti-cancer agents convert the topoisomerase II enzymes into DNA-cleaving toxins which are currently are area of research interest.[2]
Les produits sont destinés à la recherche uniquement. Ne pas utiliser chez l'homme. Nous ne vendons pas aux patients.
©Copyright 2013 Selleck Chemicals. Tous droits réservés.