Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Tyrphostin AG 494 blocks Cdk2 activation

N Osherov1, A Levitzki

  • 1Department of Biological Chemistry, Alexander Silverman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Israel.

FEBS Letters
|June 30, 1997
PubMed
Summary

The tyrphostin AG 494 compound inhibits cell proliferation by blocking Cdk2 activation, not EGFR kinase, in intact cells. This finding suggests AG 494 and analogs are potential drug leads for cell cycle machinery targets.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

<i>Aspergillus fumigatus</i> and aspergillosis: From basics to clinics.

Studies in mycology·2021
Same author

Targeting colorectal cancer via its microenvironment by inhibiting IGF-1 receptor-insulin receptor substrate and STAT3 signaling.

Oncogene·2015
Same author

Targeting melanoma with NT157 by blocking Stat3 and IGF1R signaling.

Oncogene·2015
Same author

Status of p53 in human cancer cells does not predict efficacy of CHK1 kinase inhibitors combined with chemotherapeutic agents.

Oncogene·2010
Same author

Aspergillus strain typing in the genomics era.

Studies in mycology·2008
Same author

Cisplatin induces PKB/Akt activation and p38(MAPK) phosphorylation of the EGF receptor.

Oncogene·2006

Area of Science:

  • Cell Biology
  • Biochemistry
  • Pharmacology

Background:

  • The EGFR kinase selective tyrphostin AG 494 inhibits cell proliferation but not EGFR kinase in intact cells.
  • This suggests a mechanism independent of direct EGFR kinase inhibition for AG 494's anti-proliferative effects.

Purpose of the Study:

  • To investigate the molecular mechanism by which AG 494 inhibits cell proliferation.
  • To evaluate the effect of AG 494 and its analogs on Cdk2 activation.

Main Methods:

  • Treatment of cells with AG 494, AG 490, AG 555, and AG 1478.
  • Assessment of Cdk2 activation and DNA synthesis.
  • Comparison of inhibitory effects on Cdk2 activation and cell proliferation.

Main Results:

  • AG 494, AG 490, and AG 555 block Cdk2 activation, while AG 1478 does not.
  • AG 494 inhibits Cdk2 activation even when added 20 hours after EGF stimulation.
  • Inhibitory activity on Cdk2 activation correlates with DNA synthesis inhibition.

Conclusions:

  • AG 494's anti-proliferative effect is mediated by Cdk2 activation inhibition, not direct EGFR kinase blockade.
  • AG 494 and its analogs show promise as lead compounds for developing drugs targeting the cell cycle machinery.

Related Experiment Videos