Disease relevance of NSC606170

• Analysis of HIV-1 variants confirmed that the ddI resistance mutation alone conferred ddI and 2',3'-dideoxycytidine resistance, and suppressed the effect of the AZT resistance mutation [1].
• Several dideoxynucleosides have been shown to have potent in vitro and, in the case of 3'-azido-2',3'-dideoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC), in vivo activity against HIV [2].
• Five dose regimens of 2',3'-dideoxycytidine (ddC) were administered, intravenously for 2 weeks then orally for 4 or more weeks, to 20 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). ddC was well absorbed from the gut and crossed the blood-brain barrier [3].
• Inhibition of duck hepatitis B virus replication by 2',3'-dideoxycytidine. A potent inhibitor of reverse transcriptase [4].
• OBJECTIVE: To determine whether alternating regimens consisting of zidovudine and 2',3'-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone [5].

High impact information on NSC606170

• The nucleoside analogue, 2',3'-dideoxycytidine (ddC), is a potent inhibitor of HIV replication, and AIDS patients receiving ddC experience clinical improvement without significant hematologic toxicity [6].
• The effect of 2',3'-dideoxycytidine, a potent antiviral agent, which, following anabolic phosphorylation, inhibits the reverse transcriptase of the human immunodeficiency virus in vitro, was assessed in 16 Pekin ducks chronically infected with the duck hepatitis B virus [4].
• Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2',3'-dideoxycytidine 5'-triphosphate and other drugs [7].
• Human immunodeficiency virus type 1 (HIV-1) strains were isolated from nine patients before and after prolonged therapy with either an alternating regimen of 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC) (AZT/ddC) or 2',3'-dideoxyinosine (ddI) alone [8].
• A prototype of these drugs in a form already phosphorylated (2',3'-dideoxycytidine 5'-triphosphate; ddCTP) was encapsulated into erythrocytes [9].

Chemical compound and disease context of NSC606170

• Allelotype analysis of 2',3'-dideoxycytidine- and 1,3-butadiene-induced lymphomas in B6C3F1 mice [10].
• Novel mutation in the human immunodeficiency virus type 1 reverse transcriptase gene that encodes cross-resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine [11].
• Anti-human immunodeficiency virus type 1 therapy and peripheral neuropathy: prevention of 2',3'-dideoxycytidine toxicity in PC12 cells, a neuronal model, by uridine and pyruvate [12].
• A human immunodeficiency virus type 1 variant resistant to zalcitabine (2',3'-dideoxycytidine [ddC]) was selected by sequential passage in the presence of increasing concentrations of ddC in peripheral blood mononuclear cell cultures [13].
• 2',3'-Dideoxythymidine (ddT) and 2',3'-dideoxy-2',3'-didehydrothymidine (D4T) induced sulA at 100 to 1,000 micrograms/ml, while 2',3'-dideoxycytidine (ddC) weakly induced prophage lambda [14].

Biological context of NSC606170

• Unlike 2',3'-dideoxycytidine, these two compounds do not affect mitochondrial DNA synthesis in cells at concentrations lower than that required to inhibit cell growth [15].
• Both 2',3'-dideoxyadenosine and 2',3'-dideoxycytidine appear to completely block reverse transcription from viral RNA to viral DNA [16].
• Early replicative intermediates of lambda dv plasmid were prepared by an in vitro replication system in the presence of 2',3'-dideoxycytidine 5'-triphosphate, an inhibitor of DNA chain elongation [17].
• A selective and irreversible inhibition of DHBV DNA replication is found in ducklings treated with high doses of ddDAPR (20 to 50 mg/kg), but not with similar doses of 2',3'-dideoxycytidine (ddC) [18].
• To identify potential tumor suppressor genes involved in lymphoma development, we generated allelotypes of 16 2',3'-dideoxycytidine (ddC and 31 1,3-butadiene (BD)-induced lymphomas from C57BL/6 x C3H/He F1 (hereafter called B6C3F1) mice [10].

Anatomical context of NSC606170

• In order to identify the molecular basis for dCK deficiency in two clonal T-lymphoblast cell lines generated by virtue of their resistance to 1-beta-D-arabinofuranosylcytosine (ara-C-8D) or to 2',3'-dideoxycytidine (ddC50), we have cloned and sequenced their dCK complementary DNAs [19].
• The nucleoside analog 2',3'-dideoxycytidine (ddCyd) has been shown to inhibit the infectivity and cytopathic effect of human immunodeficiency virus on human OKT4+ lymphocytes in vitro [20].
• Expression of cN-I also conferred a 22-fold increase in the IC(50) to 2',3'-difluorodeoxycytidine in HEK 293 cells and an 82-fold increase in the IC(50) to 2',3'-dideoxycytidine in Jurkat cells [21].
• Transport of the antiviral nucleoside analogs 3'-azido-3'-deoxythymidine and 2',3'-dideoxycytidine by a recombinant nucleoside transporter (rCNT) expressed in Xenopus laevis oocytes [22].
• 2',3'-Dideoxycytidine alters calcium buffering in cultured dorsal root ganglion neurons [23].

Associations of NSC606170 with other chemical compounds

• The H+-coupled hCNT3 did not transport guanosine or 3'-azido-3'-deoxythymidine and 2',3'-dideoxycytidine, demonstrating that Na+- and H+-bound versions of hCNT3 have significantly different conformations of the nucleoside binding pocket and/or translocation channel [24].
• The toxic effects of various concentrations of 2',3'-dideoxycytidine (ddC), 2',3'-dideoxy-2',3'-didehydrothymidine (D4T), and 2',3'-dideoxyinosine (ddI) on CEM cells after 4 days of culture were assessed by measuring cell viability, mitochondrial DNA (mtDNA) content, and mitochondrial morphology [25].
• Pharmacokinetics and distribution over the blood-brain barrier of zalcitabine (2',3'-dideoxycytidine) and BEA005 (2', 3'-dideoxy-3'-hydroxymethylcytidine) in rats, studied by microdialysis [26].
• Deoxycytidine and 2',3'-dideoxycytidine metabolism in human monocyte-derived macrophages. A study of both anabolic and catabolic pathways [27].
• The effect of hydroxyurea (HU) on cell growth, cell cycle progression, and the intracellular accumulation of 2',3'-dideoxycytidine (ddC) and ddCTP formation was examined [28].

Gene context of NSC606170

• The p15INK4b promoter region was hypermethylated in two additional 2',3'-dideoxycytidine-induced lymphomas [29].
• Although the p16INK4a-alpha gene appeared normal in DNA from 2',3'-dideoxycytidine-induced lymphomas, Southern analyses revealed homozygous deletions or rearrangements of the p16INK4a-beta and/or p15INK4b genes in four of 16 tumours [29].
• Mutation analysis of the pRb pathway in 2',3'-dideoxycytidine- and 1, 3-butadiene-induced mouse lymphomas [30].
• Mutations in ras and p53 genes are relatively infrequent in 2',3'-dideoxycytidine-induced lymphomas, suggesting that other genes must be involved [31].
• Genetic alterations of p53 and ras genes in 1,3-butadiene- and 2',3'-dideoxycytidine-induced lymphomas [31].

Analytical, diagnostic and therapeutic context of NSC606170

• The compound 2',3'-dideoxycytidine (ddC) is a potent inhibitor of human immunodeficiency virus replication in vitro and is currently in clinical trials for treatment of acquired immunodeficiency syndrome [32].
• We administered the antiviral agent 2',3'-dideoxycytidine (ddC) to HIV-infected patients with either ARC or AIDS as part of the AIDS Clinical Treatment Group protocol 012 and serially evaluated them with neuropathic symptom questionnaires, neurologic examinations, nerve conduction studies, and quantitative sensory testing (QST) [33].
• In vitro and in vivo evidence that the antiviral activity of 2',3'-dideoxycytidine is target cell dependent in a feline retrovirus animal model [34].
• Human red blood cells as bioreactors for the release of 2',3'-dideoxycytidine, an inhibitor of HIV infectivity [35].
• The experimental anti-AIDS glycerophosphatidic acid: nucleoside (sn-1/sn-2 diacylglycerol:dideoxynucleotide) drugs 3'-azido-3'-deoxythymidine monophosphate diglyceride (AZT-MP-DG) and 2',3'-dideoxycytidine monophosphate diglyceride (ddC-MP-DG) were isolated and purified by reversed-phase high-performance liquid chromatography (HPLC) [36].

References