zalcitabine

Summary

Summary: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy.

Top Publications

  1. Joseph E, Levine J. Caspase signalling in neuropathic and inflammatory pain in the rat. Eur J Neurosci. 2004;20:2896-902 pubmed
    ..This suggests that these pathways are potential targets for novel pharmacological agents for the treatment of inflammatory as well as neuropathic pain. ..
  2. Lim S, Copeland W. Differential incorporation and removal of antiviral deoxynucleotides by human DNA polymerase gamma. J Biol Chem. 2001;276:23616-23 pubmed
    ..Thus, although their greatest inhibitory effects are through incorporation and chain termination, persistence of these analogs in DNA and inhibition of exonucleolytic proofreading may also contribute to mitochondrial toxicity. ..
  3. Feng J, Johnson A, Johnson K, Anderson K. Insights into the molecular mechanism of mitochondrial toxicity by AIDS drugs. J Biol Chem. 2001;276:23832-7 pubmed
    ..Among the AIDS drugs approved by the FDA for clinical use, two are modified cytosine analogs, Zalcitabine (2',3'-dideoxycytidine (ddC)) and Lamivudine (beta-d-(+)-2',3'-dideoxy-3'-thiacytidine ((-)3TC]))...
  4. Brown T, Clayton D. Release of replication termination controls mitochondrial DNA copy number after depletion with 2',3'-dideoxycytidine. Nucleic Acids Res. 2002;30:2004-10 pubmed
    ..However, termination of D-loop strand synthesis is persistent, indicating formation of the D-loop structure has a purpose that is required under conditions of rapid recovery of depleted mtDNA. ..
  5. Lebrecht D, Vargas Infante Y, Setzer B, Kirschner J, Walker U. Uridine supplementation antagonizes zalcitabine-induced microvesicular steatohepatitis in mice. Hepatology. 2007;45:72-9 pubmed
    b>Zalcitabine is an antiretroviral nucleoside analogue that exhibits long-term toxicity to hepatocytes by interfering with the replication of mitochondrial DNA (mtDNA). Uridine antagonizes this effect in vitro...
  6. Bhangoo S, Ren D, Miller R, Chan D, Ripsch M, Weiss C, et al. CXCR4 chemokine receptor signaling mediates pain hypersensitivity in association with antiretroviral toxic neuropathy. Brain Behav Immun. 2007;21:581-91 pubmed
    ..Increased numbers of CXCR4 receptors would also explain the synergism observed between NRTI treatment and the proalgesic effects of HIV-1 infection. ..
  7. Idoko J, Akinsete L, Abalaka A, Keshinro L, Dutse L, Onyenekwe B, et al. A multicentre study to determine the efficacy and tolerability of a combination of nelfinavir (VIRACEPT), zalcitabine (HIVID) and zidovudine in the treatment of HIV infected Nigerian patients. West Afr J Med. 2002;21:83-6 pubmed
    ..The study has therefore demonstrated the significant efficacy and tolerability of (Nelfinavir/Zalcitabine/ Zidovudine combination in suppressing viral replication, increasing the CD4 cell counts and improving the ..
  8. Wallace V, Blackbeard J, Segerdahl A, Hasnie F, Pheby T, McMahon S, et al. Characterization of rodent models of HIV-gp120 and anti-retroviral-associated neuropathic pain. Brain. 2007;130:2688-702 pubmed
    ..in the peripheral and central nervous system following systemic treatment with the anti-retroviral agent, ddC (Zalcitabine) with or without the concomitant delivery of HIV-gp120 to the rat sciatic nerve (gp120+ddC)...
  9. Balzarini J, Pauwels R, Baba M, Herdewijn P, De Clercq E, Broder S, et al. The in vitro and in vivo anti-retrovirus activity, and intracellular metabolism of 3'-azido-2',3'-dideoxythymidine and 2',3'-dideoxycytidine are highly dependent on the cell species. Biochem Pharmacol. 1988;37:897-903 pubmed
    ..Thus, much higher ddCTP than AzddTTP levels were achieved in human lymphoid cells, an observation that may be particularly relevant from a therapeutic viewpoint. ..

More Information

Publications62

  1. Walker U, Bäuerle J, Laguno M, Murillas J, Mauss S, Schmutz G, et al. Depletion of mitochondrial DNA in liver under antiretroviral therapy with didanosine, stavudine, or zalcitabine. Hepatology. 2004;39:311-7 pubmed
    The "D drug" HIV reverse-transcriptase inhibitors zalcitabine, didanosine, and stavudine are relatively strong inhibitors of polymerase-gamma compared with the "non-D drugs" zidovudine, lamivudine, and abacavir...
  2. Joseph E, Levine J. Mitochondrial electron transport in models of neuropathic and inflammatory pain. Pain. 2006;121:105-14 pubmed
    ..These experiments demonstrate a role of the mitochondrial electron transport chain in neuropathic and some forms of inflammatory pain. The contribution of the mitochondrial electron transport chain in neuropathic pain is ATP dependent. ..
  3. Lund K, Peterson L, Wallace K. Absence of a universal mechanism of mitochondrial toxicity by nucleoside analogs. Antimicrob Agents Chemother. 2007;51:2531-9 pubmed
    ..7 and 13.4 microg/ml), didanosine (ddI) (10 and 50 microM; 2.4 and 11.8 microg/ml), and zalcitabine (ddC) (1 and 5 microM; 0.21 and 1...
  4. Sangkitporn S, Shide L, Klinbuayaem V, Leenasirimakul P, Wirayutwatthana N, Leechanachai P, et al. Efficacy and safety of zidovudine and zalcitabine combined with a combination of herbs in the treatment of HIV-infected Thai patients. Southeast Asian J Trop Med Public Health. 2005;36:704-8 pubmed
    ..controlled trial to determine the efficacy and safety of combined-herbs (SH) given with zidovudine (ZDV) and zalcitabine (ddC) for the treatment of HIV infection in Thai adults was conducted in 3 hospitals in northern Thailand ..
  5. Dalakas M, Semino Mora C, Leon Monzon M. Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2'3'-dideoxycytidine (ddC). Lab Invest. 2001;81:1537-44 pubmed
  6. Revicki D, Moyle G, Stellbrink H, Barker C. Quality of life outcomes of combination zalcitabine-zidovudine, saquinavir-zidovudine, and saquinavir-zalcitabine-zidovudine therapy for HIV-infected adults with CD4 cell counts between 50 and 350 per cubic millimeter. PISCES (SV14604) Study Group. AIDS. 1999;13:851-8 pubmed
    This double-blind study evaluated treatment with zalcitabine-zidovudine, saquinavir-zidovudine, or saquinavir-zalcitabine-zidovudine on the health-related quality of life of HIV-infected adults with CD4 cell counts between 50 and 350 ..
  7. Revicki D, Swartz C, Wu A, Haubrich R, Collier A. Quality of life outcomes of saquinavir, zalcitabine and combination saquinavir plus zalcitabine therapy for adults with advanced HIV infection with CD4 counts between 50 and 300 cells/mm3. Antivir Ther. 1999;4:35-44 pubmed
    ..This double-blind study evaluated zalcitabine or saquinavir monotherapy and combination saquinavir plus zalcitabine therapy on HROL of human immunodeficiency ..
  8. Wallace V, Segerdahl A, Lambert D, Vandevoorde S, Blackbeard J, Pheby T, et al. The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on pain behaviour in rodent models of neuropathy. Br J Pharmacol. 2007;151:1117-28 pubmed
    ..This presents L-29 as a novel analgesic compound that may target the endogenous cannabinoid system while avoiding undesirable side effects associated with direct cannabinoid receptor activation. ..
  9. Karlsson A, Söderkvist P, Zhuang S. Point mutations and deletions in the znfn1a1/ikaros gene in chemically induced murine lymphomas. Cancer Res. 2002;62:2650-3 pubmed
    ..Our results suggest inactivation of Ikaros in a subset of chemically induced lymphomas and additionally support the contention of tumor-suppressor activity for Ikaros. ..
  10. Morris G, LaClair D, McKee E. Pyrimidine deoxynucleoside and nucleoside reverse transcriptase inhibitor metabolism in the perfused heart and isolated mitochondria. Antivir Ther. 2010;15:587-97 pubmed publisher
  11. Sax P. Meeting notes from ICAAC. D-D4FC (Reverset): further data on treatment-experienced patients. AIDS Clin Care. 2005;17:8 pubmed
  12. López Bernaldo de Quirós J. [Tenofovir DF in rescue regimens]. Enferm Infecc Microbiol Clin. 2008;26 Suppl 8:25-30 pubmed
    ..This mutation was selected by treatments with zalcitabine monotherapy...
  13. Agarwal R, Han T, Fernandez M. Collateral resistance of a dideoxycytidine-resistant cell line to 5-fluoro-2'-deoxyuridine. Biochem Biophys Res Commun. 1999;262:657-60 pubmed
    ..2% in these cell lines. Taken together, the data suggest that ddC, an antiviral agent, is capable of inducing resistance to FdUR-a drug that is not its analog and which has a different metabolism, target site, and mechanism of action. ..
  14. Fujinaga M, Schulte M, Holodniy M. Assessment of developmental toxicity of antiretroviral drugs using a rat whole embryo culture system. Teratology. 2000;62:108-14 pubmed
    ..No growth retardation or gross morphologic abnormalities were found for any of the agents, either singly or in combination, at clinically relevant concentrations. ..
  15. Hanes J, Johnson K. Exonuclease removal of dideoxycytidine (zalcitabine) by the human mitochondrial DNA polymerase. Antimicrob Agents Chemother. 2008;52:253-8 pubmed
    ..Here we show that the rate of excision of dideoxycytidine (zalcitabine; ddC) was reduced fourfold (giving a half-life of approximately 2...
  16. Ganser A, Greher J, Völkers B, Staszewski S, Hoelzer D. Inhibitory effect of azidothymidine, 2'-3'-dideoxyadenosine, and 2'-3'-dideoxycytidine on in vitro growth of hematopoietic progenitor cells from normal persons and from patients with AIDS. Exp Hematol. 1989;17:321-5 pubmed
    ..The inhibition of progenitor cells from AIDS patients by the 2'-3'-dideoxynucleosides was comparable to normal progenitors, except for a higher sensitivity of AIDS-derived CFU-GEMM and BFU-E to AZT. ..
  17. van Wijk G, Hostetler K, van den Bosch H. Antiviral nucleoside diphosphate diglycerides: improved synthesis and facilitated purification. J Lipid Res. 1992;33:1211-9 pubmed
    ..In addition, the purification of the compounds is greatly facilitated due to the small amount of phosphatidic acid remaining in the reaction mixture. ..
  18. Desmaele D, Gref R, Couvreur P. Squalenoylation: a generic platform for nanoparticular drug delivery. J Control Release. 2012;161:609-18 pubmed publisher
    ..e. "Nanotheragnostics"). This new nanotechnology platform is expected to have important applications in pharmacology. ..
  19. Brennan T, Taylor D, Bridges C, Leyda J, Tyms A. The inhibition of human immunodeficiency virus type 1 in vitro by a non-nucleoside reverse transcriptase inhibitor MKC-442, alone and in combination with other anti-HIV compounds. Antiviral Res. 1995;26:173-87 pubmed
    ..The use of MKC-442 in a two- or three-drug combination regimen with other RT inhibitors, a proteinase inhibitor or an alpha-glucosidase 1 inhibitor should be considered for HIV-1-related chemotherapy. ..
  20. Gray N, Marr C, Penn C, Cameron J, Bethell R. The intracellular phosphorylation of (-)-2'-deoxy-3'-thiacytidine (3TC) and the incorporation of 3TC 5'-monophosphate into DNA by HIV-1 reverse transcriptase and human DNA polymerase gamma. Biochem Pharmacol. 1995;50:1043-51 pubmed
    ..This may explain the low levels of mitochondrial toxicity observed with 3TC. ..
  21. Autran B, Carcelain G, Li T, Blanc C, Mathez D, Tubiana R, et al. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science. 1997;277:112-6 pubmed
    ..Thus, decreasing the HIV load can reverse HIV-driven activation and CD4(+) T cell defects in advanced HIV-infected patients. ..
  22. Schmit J, Ruiz L, Stuyver L, Van Laethem K, Vanderlinden I, Puig T, et al. Comparison of the LiPA HIV-1 RT test, selective PCR and direct solid phase sequencing for the detection of HIV-1 drug resistance mutations. J Virol Methods. 1998;73:77-82 pubmed
    ..Overall, there was a 73 to 100% concordance between the three methods. In this study, LiPA HIV-1 RT proved to be an accurate and reliable alternative to DNA sequencing for the detection of drug resistance mutations in patient samples. ..
  23. Spikings E, Alderson J, St John J. Regulated mitochondrial DNA replication during oocyte maturation is essential for successful porcine embryonic development. Biol Reprod. 2007;76:327-35 pubmed
    ..We therefore conclude that adherence to the regulation of the timing of mtDNA replication during oocyte maturation is essential for successful embryonic development. ..
  24. Lund K, Wallace K. Adenosine 3',5'-cyclic monophosphate (cAMP)-dependent phosphoregulation of mitochondrial complex I is inhibited by nucleoside reverse transcriptase inhibitors. Toxicol Appl Pharmacol. 2008;226:94-106 pubmed
  25. Susman E. HIV Pathogenesis and Treatment - Third International AIDS Society Conference. IDrugs. 2005;8:813-5 pubmed
  26. Kumamoto H, Onuma S, Tanaka H, Dutschman G, Cheng Y. 3'-Carbon-substituted pyrimidine nucleosides having a 2',3'-dideoxy and 2',3'-didehydro-2',3'-dideoxy structure: synthesis and antiviral evaluation. Antivir Chem Chemother. 2006;17:225-34 pubmed
    ..Some 2',3'-dideoxycytidine (ddC) analogues were also synthesized. Antiviral evaluation revealed that none of these analogues showed activity against HIV, hepatitis B virus, herpes simplex virus-1 (HSV-1) and HSV-2. ..
  27. Carruth L, Zink M, Tarwater P, Miller M, Li M, Queen L, et al. SIV-specific T lymphocyte responses in PBMC and lymphoid tissues of SIV-infected pigtailed macaques during suppressive combination antiretroviral therapy. J Med Primatol. 2005;34:109-21 pubmed
    ..Conversely, in the setting of low initial viremia and robust T lymphocyte responses, treatment does not have a detrimental effect on the immune response. ..
  28. Pohjoismäki J, Wanrooij S, Hyvärinen A, Goffart S, Holt I, Spelbrink J, et al. Alterations to the expression level of mitochondrial transcription factor A, TFAM, modify the mode of mitochondrial DNA replication in cultured human cells. Nucleic Acids Res. 2006;34:5815-28 pubmed
    ..We propose that TFAM influences the mode of mtDNA replication via its combined effects on different aspects of mtDNA metabolism. ..
  29. Skopelitis E, Kokotis P, Kontos A, Panayiotakopoulos G, Konstantinou K, Kordossis T, et al. Distal sensory polyneuropathy in HIV-positive patients in the HAART era: an entity underestimated by clinical examination. Int J STD AIDS. 2006;17:467-72 pubmed
    ..Age, severe prior immunosuppression and the combined use of zalcitabine (ddC), stavudine (d4T) and didanosine (ddI) are important risk factors.
  30. Gerber M, Breytenbach J, du Plessis J. Transdermal penetration of zalcitabine, lamivudine and synthesised N-acyl lamivudine esters. Int J Pharm. 2008;351:186-93 pubmed
    The objective of this study was to determine the in vitro transdermal permeation through human epidermis of zalcitabine, lamivudine and the synthesised N-acyl lamivudine esters, with and without the use of Pheroid as delivery system and ..
  31. Macher A, Thomas D, Paul S. Contraindicated antiretroviral drug combinations. N J Med. 2003;100:41-3; quiz 73-4 pubmed
    ..stavudine plus zidovudine; 2. Invirase plus two nucleoside analog reverse transcriptase inhibitors (NRTIS); 3. zalcitabine plus didanosine; 4. zalcitabine plus stavudine; and, 5. zalcitabine plus lamivudine...
  32. Gustavson L, Fukuda E, Rubio F, Dunton A. A pilot study of the bioavailability and pharmacokinetics of 2',3'-dideoxycytidine in patients with AIDS or AIDS-related complex. J Acquir Immune Defic Syndr. 1990;3:28-31 pubmed
    ..It is also rapidly eliminated with a half-life of 1-2 h. There are no apparent differences in the absorption or elimination of ddC between 0.5 and 5 mg oral doses. ..
  33. Lang W, Osmond D, Page Bodkin K, Moss A, Winkelstein W. Population-based estimates of antiretroviral therapy and anti-Pneumocystis prophylaxis in San Francisco: 1991. J Acquir Immune Defic Syndr. 1993;6:191-5 pubmed
    ..Compared with 1987-1989, there were substantial increases in both antiretroviral therapy and anti-Pneumocystis prophylaxis use. ..
  34. Minkoff H, Augenbraun M. Antiretroviral therapy for pregnant women. Am J Obstet Gynecol. 1997;176:478-89 pubmed
  35. Adkins J, Peters D, Faulds D. Zalcitabine. An update of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of HIV infection. Drugs. 1997;53:1054-80 pubmed
    b>Zalcitabine is a dideoxynucleoside antiretroviral agent that is phosphorylated to the active metabolite 2',3'-dideoxycytidine 5'-triphosphate (ddCTP) within both uninfected and HIV-infected cells...
  36. Parker W, Shaddix S, Vince R, Bennett L. Lack of mitochondrial toxicity in CEM cells treated with carbovir. Antiviral Res. 1997;34:131-6 pubmed
  37. Izopet J, Tamalet C, Pasquier C, Sandres K, Marchou B, Massip P, et al. Quantification of HIV-1 proviral DNA by a standardized colorimetric PCR-based assay. J Med Virol. 1998;54:54-9 pubmed
    ..The reliability of this simple and convenient colorimetric PCR-based technique indicates its suitability for assessing the effect of current antiretroviral regimens on the latent reservoirs of provirus. ..
  38. Fiscus S, Hughes M, Lathey J, Pi T, Jackson B, Rasheed S, et al. Changes in virologic markers as predictors of CD4 cell decline and progression of disease in human immunodeficiency virus type 1-infected adults treated with nucleosides. AIDS Clinical Trials Group Protocol 175 Team. J Infect Dis. 1998;177:625-33 pubmed
    ..Plasma HIV-1 RNA appears to be the best predictor of long-term CD4 cell count responses and disease progression. ..
  39. Borg N, Stahle L. 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. Antimicrob Agents Chemother. 1998;42:2174-7 pubmed
    ..applied to sample the unbound drug concentration in the extracellular fluid in brain and muscle of rats given zalcitabine (2',3'-dideoxycytidine; n = 4) or BEA005 (2', 3'-dideoxy-3'-hydroxymethylcytidine; n = 4) (50 mg/kg of body ..
  40. Winters M, Coolley K, Girard Y, Levee D, Hamdan H, Shafer R, et al. A 6-basepair insert in the reverse transcriptase gene of human immunodeficiency virus type 1 confers resistance to multiple nucleoside inhibitors. J Clin Invest. 1998;102:1769-75 pubmed
    ..These results establish that inserts, like point mutations, are selected in vivo during antiretroviral therapy and provide resistance to multiple nucleoside analogs. ..
  41. Lake Bakaar G, Mazzoccoli V, Dickman K, Lyubsky S. Differential effects of nucleoside analogs on oxidative phosphorylation in human pancreatic cells. Dig Dis Sci. 2001;46:1853-63 pubmed
    ..However, the mitochondrial phenotypic damage induced by ddI and ddA appear to result in less Capan-1 cytotoxicity than ddC and d4T. The link between these differential effects and ddI pancreatitis is unclear. ..
  42. Stuyver L, Lostia S, Adams M, Mathew J, Pai B, Grier J, et al. Antiviral activities and cellular toxicities of modified 2',3'-dideoxy-2',3'-didehydrocytidine analogues. Antimicrob Agents Chemother. 2002;46:3854-60 pubmed
    ..08 micro M) and lamivudine-resistant HIV-1 (EC(90) = 0.15 micro M) is markedly reduced by introduction of a 3'-fluorine in the sugar (EC(90)s of compound 2a, 37.5 and 494 micro M, respectively). ..
  43. Geleziunas R, Gallagher K, Zhang H, Bacheler L, Garber S, Wu J, et al. HIV-1 resistance profile of the novel nucleoside reverse transcriptase inhibitor beta-D-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine (Reverset). Antivir Chem Chemother. 2003;14:49-59 pubmed
    ..3- to 8.7-fold resistance to D-d4FC in vitro. These findings suggest that D-d4FC may represent an alternative NRTI for the treatment of individuals infected with lamivudine- and zidovudine-resistant strains of HIV-1. ..
  44. Ghosh D. Semiparametric analysis of recurrent events: artificial censoring, truncation, pairwise estimation and inference. Lifetime Data Anal. 2010;16:509-24 pubmed publisher
    ..New resampling-based methods for variance estimation and model checking are also described. The methods are illustrated by application to data from an HIV clinical trial as with a limited simulation study. ..
  45. Otto M. New nucleoside reverse transcriptase inhibitors for the treatment of HIV infections. Curr Opin Pharmacol. 2004;4:431-6 pubmed
    ..Clinical trials are demonstrating that some of these goals are being met, and that nucleoside analogs as a class of compounds remain fertile ground for finding valuable additions to current anti-retrovirus treatment regimens. ..
  46. Liu J, Wang Q, Wang B, Xuan X, Chen Q, Xu D, et al. [The curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2011;29:98-102 pubmed
  47. Amancha P, Hong J, Rogers K, Ansari A, Villinger F. In vivo blockade of the programmed cell death-1 pathway using soluble recombinant PD-1-Fc enhances CD4+ and CD8+ T cell responses but has limited clinical benefit. J Immunol. 2013;191:6060-70 pubmed publisher
  48. Stuyver L, McBrayer T, Schurmann D, Kravec I, Beard A, Cartee L, et al. Potent antiviral effect of reverset in HIV-1-infected adults following a single oral dose. Antivir Ther. 2004;9:529-36 pubmed
    ..A single 10 mg RVT dose resulted in a viral load drop of 0.61 +/- 0.05 log10 providing evidence that a viral strain with the indicated genotype is susceptible to RVT. ..
  49. Hill S, Lloyd P, McDonald S, Wykoff J, Derse D. Susceptibility of human T cell leukemia virus type I to nucleoside reverse transcriptase inhibitors. J Infect Dis. 2003;188:424-7 pubmed
    ..The susceptibility of HTLV-I to 6 nucleoside reverse-transcriptase inhibitors was examined. HTLV-I replication was inhibited by tenofovir, abacavir, lamivudine, zalcitabine, stavudine, and zidovudine.
  50. Erickson Viitanen S, Wu J, Shi G, Unger S, King R, Fish B, et al. Cellular pharmacology of D-d4FC, a nucleoside analogue active against drug-resistant HIV. Antivir Chem Chemother. 2003;14:39-47 pubmed
  51. Le Guerhier F, Pichoud C, Jamard C, Guerret S, Chevallier M, Peyrol S, et al. Antiviral activity of beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine in woodchucks chronically infected with woodchuck hepatitis virus. Antimicrob Agents Chemother. 2001;45:1065-77 pubmed
    ..These results indicate that beta-L-Fd4C exhibits a more potent antiviral effect than lamivudine in the WHV model but was not able to eradicate CCC DNA and infected cells from the liver at the dosage and with the protocol used. ..
  52. Johnson M, Johns D, Fridland A. 2',3'-Dideoxynucleoside phosphorylation by deoxycytidine kinase from normal human thymus extracts: activation of potential drugs for AIDS therapy. Biochem Biophys Res Commun. 1987;148:1252-8 pubmed
    ..Thus, dideoxynucleosides are activated by deoxycytidine kinase through a different catalytic interaction than occurs in 5'-activation of 3'-hydroxynucleosides by this enzyme. ..
  53. Zeidner N, Strobel J, Perigo N, Hill D, Mullins J, Hoover E. Treatment of FeLV-induced immunodeficiency syndrome (FeLV-FAIDS) with controlled release capsular implantation of 2',3'-dideoxycytidine. Antiviral Res. 1989;11:147-60 pubmed
    ..Initial clinical trials employing controlled release capsular ddC implants in vivo indicate significant retardation of FeLV-FAIDS replication throughout a four week treatment period. ..