Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Intracellular Metabolism of CycloSaligenyl 3′-Azido-2′,3′-dideoxythymidine Monophosphate, a Prodrug of 3′-Azido-2′,3′-dideoxythymidine (Zidovudine)

Jan Balzarini, Lieve Naesens, S. Aquaro, T. Knispel, C.-F. Perno, E. De Clercq and C. Meier
Molecular Pharmacology December 1999, 56 (6) 1354-1361; DOI: https://doi.org/10.1124/mol.56.6.1354
Jan Balzarini
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lieve Naesens
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Aquaro
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
T. Knispel
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C.-F. Perno
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E. De Clercq
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. Meier
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The administration of CycloSaligenyl 3′-azido-2′,3′-dideoxythymidine monophosphate (CycloSal-AZTMP) to CEM cells resulted in a concentration- and time-dependent conversion to the 5′-monophosphate (AZTMP), 5′-diphosphate (AZTDP), and 5′-triphosphate (AZTTP) derivatives. High ratios of AZTMP/AZTTP were found in the CEM cell cultures treated with CycloSal-AZTMP. The intracellularT 1/2 of AZTTP in CEM cell cultures treated with either AZT and CycloSal-AZTMP was approximately 3 h. A variety of human T- and B-lymphocyte cell lines efficiently converted the prodrug to the AZT metabolites, whereas peripheral blood lymphocytes and primary monocyte/macrophages showed at least 10-fold lower metabolic conversion of the prodrug.CycloSal-AZTMP failed to generate marked levels of AZT metabolites in thymidine kinase-deficient CEM/TK− cells, an observation that is in agreement with the substantial loss of antiviral activity of CycloSal-AZTMP in CEM/TK− cells. The inability ofCycloSal-AZTMP to generate AZTMP in CEM/TK−cells is presumably due to a relatively high hydrolysis rate of AZTMP to the parent nucleoside AZT, combined with the inability of CEM/TK− cells to phosphorylate AZT to AZTMP through the cytosolic salvage enzyme thymidine kinase.

Footnotes

    • Received July 2, 1999.
    • Accepted September 9, 1999.
  • Send reprint requests to: Prof. Dr. J. Balzarini, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium. E-mail: jan.balzarini{at}rega.kuleuven.ac.be

  • This work was supported by Biomedical Research Programme of the European Commission, the Belgian “Geconcerteerde Onderzoeksacties” (Project 95/5), and the “Fonds voor Wetenschappelijk Onderzoek–Vlaanderen” (Project G.0104.98).

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 56 (6)
Molecular Pharmacology
Vol. 56, Issue 6
1 Dec 1999
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Intracellular Metabolism of CycloSaligenyl 3′-Azido-2′,3′-dideoxythymidine Monophosphate, a Prodrug of 3′-Azido-2′,3′-dideoxythymidine (Zidovudine)
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Intracellular Metabolism of CycloSaligenyl 3′-Azido-2′,3′-dideoxythymidine Monophosphate, a Prodrug of 3′-Azido-2′,3′-dideoxythymidine (Zidovudine)

Jan Balzarini, Lieve Naesens, S. Aquaro, T. Knispel, C.-F. Perno, E. De Clercq and C. Meier
Molecular Pharmacology December 1, 1999, 56 (6) 1354-1361; DOI: https://doi.org/10.1124/mol.56.6.1354

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Intracellular Metabolism of CycloSaligenyl 3′-Azido-2′,3′-dideoxythymidine Monophosphate, a Prodrug of 3′-Azido-2′,3′-dideoxythymidine (Zidovudine)

Jan Balzarini, Lieve Naesens, S. Aquaro, T. Knispel, C.-F. Perno, E. De Clercq and C. Meier
Molecular Pharmacology December 1, 1999, 56 (6) 1354-1361; DOI: https://doi.org/10.1124/mol.56.6.1354
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Antimicrobial and Antileukemic Transportan 10 Conjugates
  • Pharmacological characterization of zebrafish H1 receptor
  • Bhave and Forman
Show more Article

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics