Ty in these animal models or patients. BMS-554417 against various human tumor xenografts in M. Although the basic mechanism of action of T araC71 75 Similar to the AraC and the DNA synthesis, there are several quantitative differences in metabolism and biochemical activity t of these two compounds which may be explained Ren differences in the anti-tumor activity of t . More importantly, Activities is the half-life of T araCTP solid tumor cells in about 10 times L Longer than araCTP, 76, and T is araCTP is a much more effective inhibitor of DNA synthesis as As araCTP.71 with gemcitabine, these two T be very important for the activity t at M mice solid tumor xenografts demonstrated.
In addition differs the interaction of T-araC with many Andarine other enzymes, with the activation of the deoxycytidine analogs parties of araC, and these differences k Can also act in vivo activity t of T-araC. With respect to ARAC and its metabolites is a poor substrate for T araC and deoxycytidine deoxycytidine deaminase activity Ten. AraCMP T is a poor substrate for dCMP Deaminaseaktivit t, but it is a better substrate for CMP / UMP kinase as araCMP, is a difference, which may at the Erl Explanation of the long half-life of T araCTP.76 Parker side Chem Rev 10 Author manuscript, increases available in PMC 2010 1 July. PA Author Manuscript NIH-PA Author Manuscript has NIH Manuscript NIH-PA Author araC as araC T only a modest effect on the activity t of ribonucleotide reductase. T araC was studied in two clinical studies to tumors77 firm to handle 78 and is currently being prepared for further clinical investigation.
T araC showed partial response in some patients with heavily pretreated relapsed solid tumors in these studies. 3.3. Sapacitabine cytosine is an analog of deoxycytidine with a structure that Is similar to the ARAC. However, instead of a 2-hydroxy CCODS has a cyano group 2 Similar to araC than deoxycytidine kinase CCODS CCODS TP, which phosphorylates a good substrate for DNA polymerases, which is involved in DNA replication. Once in the Warmth received No DNA is CCODS an elongation of the chain M not Chtig cha Have terminator.79 by DNA polymerase was strongly inhibited by the incorporation of CCODS observed in Terminal 3, which was h Ago than with gemcitabine and ARAC. If CCODS DNA is taken up in internal links, it has a secondary Greater influence on the integrity t of the DNA.
Once the Warmth DNA is extended after the formation CCODS, the phosphodiester bond between 3 and the following nucleotide CCODS not stable and the Warmth DNA is not cleaved by a spontaneous elimination, each one created not DNA ends with two C 2 is cyano, 3 didehydro 2.3 dideoxycytidine. Hence came the installation of CCODS Cha Ties can have dinner, DNA single-strand breaks in DNA. This mechanistic consideration for the design of this molecule and the dideoxy analogue into DNA of cells with CNDAC.81, 82 araC were treated as not CCODS treatment no inhibition of the activity t of ribonucleotide reductase. A derivative of palmitoyl CCODS N4 will be evaluated in clinical antitumor activity.83 3.4. The human purine nucleoside phosphorylase deficiency is a forodesine born healthy, au It that they do not produce T-cells, which then causes only one SAP