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
Abstract

Metabolic inhibition by a new antifolate, 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methyl-pyrido[2,3-d]pyrimidine (BW3O1U), an effective inhibitor of human lymphoid and dihydrofolate reductase-overproducing mouse cell lines.

W D Sedwick, M Hamrell, O E Brown and J Laszlo
Molecular Pharmacology November 1982, 22 (3) 766-770;
W D Sedwick
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M Hamrell
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
O E Brown
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J Laszlo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The human lymphoblastoid cell line, WIL-2, and a mouse cell line, 3T6R400, that overproduces a mutant dihydrofolate reductase (DHFR) having greater than 100-fold increased resistance to methotrexate (MTX) inhibition, were used to compare the inhibitory properties of a novel lipid-soluble antifolate, 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methyl-pyrido[2,3-d]pyrimidine (BW301U), with the 2,4-arylpyrimidine, 2,4-diamino-5-(3,4'-dichlorophenyl)-6-methylpyrimidine (DDMP) and with MTX. These studies demonstrated that, like DDMP, BW301U rapidly entered cells and inhibited the incorporation of dUrd into DNA. Drug association with cells was temperature-independent and apparently did not require active transport. BW301U inhibited cell growth by 50% at 0.025 microM, whereas MTX caused equivalent inhibition at 0.045 microM. Inhibition of DNA synthesis produced by 90 min of exposure to BW301U was completely reversed within 2 hr after washing cells and suspending them in drug-free medium. In contrast, inhibition of DNA synthesis in MTX-treated cells was not reversed by simply removing the antifolate, but required the addition of calcium leukovorin or thymidine to the drug-free medium in order to facilitate complete reversal of DNA synthesis. Finally, like DDMP, BW301U was approximately 1000 times more effective than MTX in inhibiting dUrd incorporation into the DNA of a DHFR gene-amplified cell line of mouse 3T6 cells.

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
Vol. 22, Issue 3
1 Nov 1982
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
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.
Metabolic inhibition by a new antifolate, 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methyl-pyrido[2,3-d]pyrimidine (BW3O1U), an effective inhibitor of human lymphoid and dihydrofolate reductase-overproducing mouse cell lines.
(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
Abstract

Metabolic inhibition by a new antifolate, 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methyl-pyrido[2,3-d]pyrimidine (BW3O1U), an effective inhibitor of human lymphoid and dihydrofolate reductase-overproducing mouse cell lines.

W D Sedwick, M Hamrell, O E Brown and J Laszlo
Molecular Pharmacology November 1, 1982, 22 (3) 766-770;

Citation Manager Formats

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

Share
Abstract

Metabolic inhibition by a new antifolate, 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methyl-pyrido[2,3-d]pyrimidine (BW3O1U), an effective inhibitor of human lymphoid and dihydrofolate reductase-overproducing mouse cell lines.

W D Sedwick, M Hamrell, O E Brown and J Laszlo
Molecular Pharmacology November 1, 1982, 22 (3) 766-770;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

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