Deoxycytidine triphosphate

Cytosine Deoxycytidine Deoxyeytidyiic acid Deoxycytidine. monophosphate (dCMP) Deoxycytidine diphosphate (dCDP) Deoxycytidine triphosphate (dCTP)... 

Gemcitabine is intracellularly activated by nucleoside kinases to diphosphate and triphosphate nucleosides. Gemcitabine diphosphate inhibits DNA synthesis by inhibiting ribonucleotide reductase while gemcitabine triphosphate competes with deoxycytidine triphosphate for incorporation into DNA. Gemcitabine is used for the treatment of non-small cell lung carcinoma and of adenocarcinoma of the pancreas. It has to be administred intravenously and is eliminated by metabolism with an elimination half-life of approximately 50 minutes. Its spectrum of adverse effects is comparable to that of 5-FU. 

Cidofovir (Vistide) is an acyclic phosphonate cytosine analogue with activity against herpesviruses including CMV, HSV-1, HSV-2, EBV, and VZV. It also inhibits adenoviruses, papillomaviruses, polyomaviruses, and poxviruses. Activation of cidofovir requires metabolism to a diphosphate by host cellular enzymes. Because this activation does not depend upon viral enzymes, similar levels of cidofovir diphosphate are seen in infected and uninfected cells. Cidofovir diphosphate competes with deoxycytidine triphosphate (dCTP) for access to viral... 

Lamivudine inhibits HBV DNA polymerase and HIVreverse transcriptase by competing with deoxycytidine triphosphate for incorporation into the viral DNA, resulting in chain termination. Lamivudine achieves 3-4 log decreases in viral replication in most patients and suppression of HBV DNA to undetectable levels in about 44% of patients. Seroconversion of HBeAg from positive to negative occurs in about 17% of patients and is durable at 3 years in about 70% of responders. Continuation of treatment for 4-8 months after seroconversion may improve the durability of response. Response in HBeAg-negative patients is initially high but less durable. 

An important difference between the two compounds is that azacytidine (2) incorporates into RNA, while decitabine (1) acts on DNA. Within cells, decitabine (1) is phosphorylated by deoxycytidine kinase, and after conversion to decitabine triphosphate, it is incorporated into DNA in place of deoxycytidine triphosphate. Azacitidine (2) is phosphorylated by uridine-cytidine kinase and eventually incorporated into RNA, inhibiting the processing of ribosomal RNA and ultimately protein synthesis. Azacitidine (2) can also inhibit DNMTs when azacytidine diphophate is reduced to decitabine diphosphate, which is further phosporylated by kinases to dcitabine triphosphate and incorporated into DNA. Because of the inefficiency of these extra steps, the hypomethylating potency of 2 is believed to be one fifth to one tenth that of l.6-8... 

In gemcitiihine, fluorine atonts replace the hydroxyl group and the hydrogen atom at the 2 position of cytidine."" After its anabolism to diphosphate and triphosphate metabolites, gemcituhine inhibits ribonucleotide mducta.se and competes with 2 -deoxycytidine triphosphate for incorporation into DN A. These effects pnxluce cell-cyclc-specific cytotoxicity. Gemcitabine has become a first-line treatment for liK ally advanced and metastatic adenocarcinoma of the pancreas. 

Analogue of deoxycytidine triphosphate, exo-N- 2-[N-(4-azido-2,5-difluoro-3 -chloropyridine-6-yl)-3 -amino-propionyl] aminoethyl -2 -deoxycytidine-5 triphosphate which has 4-azidopyridine as a photoactive site, was applied for photoaffmity modification of DNA binding proteins [111]. 

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