Therefore, , 47 and this enzyme may ZSTK474 also contribute to its activation in certain cell types. As araCTP, F araATP araGTP and are good substrates for replicative DNA polymerases. The incorporation of one or araAMP araGMP F in the 3 ‘end of DNA prevents further Verl EXTENSIONS the DNA of these enzymes, 48 50 entered Ing the inhibition of replication of DNA. Therefore, the mechanism for Abbot Tion of the cells of these three analogues arabinofuranosyl Similar. AraATP F is also a weak inhibitor of ribonucleotide reductase activity of ribonucleotide reductase.51 t of cells is tightly controlled Ensure the deoxynucleoside triphosphates by natural, that all cells deoxynucleotides necessary for DNA synthesis in the corresponding concentrations.
dATP is an important regulator of ribonucleotide reductase activity t and inhibits the reduction of ADP, UDP and F CDP.52 araATP binds to ribonucleotide reductase MLN8237 in the allosteric site of binding to an analog of dATP. As in the case of dFdC, k Nnte the inhibition of ribonucleotide reductase activity t by F araATP directed DNA polymerase activity t of this compound by reducing the intracellular Ren levels of dATP, the natural substrate coated with F araATP site for DNA polymerase competes potentiate active. The inhibition of the activity T ribonucleotide reductase does not appear to play an R The antitumor activity of t of Arag important. 45 2.3.2.2. Cladribine: Cl dAdo is an analogue of deoxyadenosine, which in 1992 for the treatment of hairy cell leukemia chemistry was admitted leukemia.
53 The sugar component of this compound is the normal deoxyribose, in contrast to arabinose, and this compound is phosphorylated by easily deoxycytidine kinase to the Cl dAdo nucleotides. Cl dATP is a good substrate for DNA polymerases, where it is taken in the heat Not growing DNA and spans arabinoside analogues such as F araA.48, 53 DNA polymerase extends slightly cha no DNA at the incorporation of a single residue Cl dAdo but was stopped by three successive stages residues.53 built dATP is dAdo Cl Cl a much more potent inhibitor of ribonucleotide reductase, which is araATP F, 48.53 and therefore, the inhibition of this enzyme to be more important mechanism of action. DFdC than araA and F, inhibition of ribonucleotide reductase can verst strengths Inhibition of nucleotide analogs by DNA polymerases.
Since the formation of three consecutive residues Dado a likely event in genome replication, k Lead nnte Cl dAdo moreover, is the interruption of the chain Not significant. AraA such as F, Cl dAdo not a substrate for adenosine deaminase, due to the presence of chlorine in the 2-position. 2.3.2.3. Clofarabine: Cl F araA was for the treatment of relapsed and refractory acute lymphoblastic leukemia admitted rem chemistry for p diatrische 2004.54,55 The structure of F Cl Cl araA differs from dAdo, there it is a fluorine atom in position 2 in the part of the deoxyribose molecule contains lt The comparison of these two drugs approved by the FDA, the best example of the FA Is that small structural differences have entered Dinner dramatic clinical differences. This small structural difference significantly increased Ht the stability t of the glycosidic bond, resulting in improved S Acid stability t of the connection and good oral bioavailability. The mechanism of action of araA F is Cl Similar to the groove-and-Cl Faraa, since it is ac