Called by deoxycytidine kinase Cl F 5 araA triphosphate, which inhibits DNA replication, as the strong inhibition of ribonucleotide reductase, and both DNA polymerase.48, 56.57 The activity t of Cl F araA with respect to the inhibition of ribonucleotide reductase is similar to the dAdo Cl. Moreover, it is easily absorbed in the heat Not SU11274 PKI-SU11274 DNA, but has a termination of the individual S not Ago as Cl F araA dAdo. Therefore, combining Cl F araA is a molecule consisting of Cl and F with the dAdo araA for their Antitumoraktivit t. As dFdC is shown Cl F araA TP that a long residence time of 56 intracellularly Ren Cl and F araA showed good activity T against many human solid Parker Page 9 Chem Rev Author manuscript, increases available in PMC 2010 1 July,.
PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Malotilate NIH tumor xenografts in mice.58 60 cl Similar Dado, Cl, F araA not a substrate for adenosine deaminase. 2.3.2.4. Pentostatin: pentostatin, Dado, such as Cl, in the treatment of hairy cell leukemia leukemia.61 chemistry is used, 62 It is a potent inhibitor of adenosine deaminase and purine or pyrimidine antimetabolite for use only approved by the FDA, the active without metabolism. ADA deficiency in humans results in a severe combined immunodeficiency syndrome by a profound deficiency of T and B cells, characterized, indicating that these cells are particularly sensitive to inhibition of this enzyme.
The inhibition of the activity of t by adenosine deaminase Pentostatin causes an increase in traffic deoxyadenosine and is responsible for the accumulation of dATP deoxyadenosine nucleotides in particular, which inhibits the activity t of inhibition of ribonucleotide reductase and DNA synthesis, because of dCTP and decrease in other substrates deoxynucleotides required for DNA synthesis. Third New connections 3.1. Troxacitabine Troxacitabine is an analogue of deoxycytidine with two unique structural features: It is a nucleoside analogue of L and it lacks both the 2 and 3 hydroxyl groups. This compound origin drug discovery efforts of nucleoside analogues that identify effective against the human immunodeficiency virus. Because deoxycytidine kinase phosphorylate the natural conformation of nucleosides L k can, 18,19 ODDC is phosphorylated very well in human cells.
However, unlike most other Similar, is the most important intracellular Re metabolites ODDC DP, 63, which is then the triphosphate form of phosphoglycerate kinase 3, no nucleoside kinase.64 converted 65 Unlike most other dideoxynucleotides, ODDC TP is a good substrate for DNA polymerase and is received in the heat No DNA, where it is an absolute necessity cha no termination because of his lack of DNA 3 OH group.66 Because of the chiral Pr conference for 3 5 exonuclease correction with DNA polymerase when incorporated into DNA is associated, not easily ODDC of the W rmequelle away no DNA, 67, although ODDC is recognized by apurinic / apyrimidinic endonuclease.68 ODDC is a very poor substrate for cytidine deaminase. ODDC has demonstrated its efficacy in malignant tumors in both solid and h Dermatological clinical trials. 69 3.2. Although Thiarabine Thiarabine is structurally Similar ARAC, the antitumor activity t of T-araC against a variety of human tumor xenografts in M Nozzles much better than that of the ARAC, 70 a compound, which does not by a solid tumor activity th