1E7-03, a low MW compound targeting host protein phosphatase-1, inhibits HIV-1 transcription


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Ammosova T. , Platonov M., Ivanov A., Kont Y. S. , Kumari N., Kehn-Hall K., ...More

BRITISH JOURNAL OF PHARMACOLOGY, vol.171, no.22, pp.5059-5075, 2014 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 171 Issue: 22
  • Publication Date: 2014
  • Doi Number: 10.1111/bph.12863
  • Title of Journal : BRITISH JOURNAL OF PHARMACOLOGY
  • Page Numbers: pp.5059-5075

Abstract

Background and PurposeHIV-1 transcription is activated by the Tat protein which recruits the cyclin-dependent kinase CDK9/cyclin T1 to TAR RNA. Tat binds to protein phosphatase-1 (PP1) through the Q(35)VCF(38) sequence and translocates PP1 to the nucleus. PP1 dephosphorylates CDK9 and activates HIV-1 transcription. We have synthesized a low MW compound 1H4, that targets PP1 and prevents HIV-1 Tat interaction with PP1 and inhibits HIV-1 gene transcription. Here, we report our further work with the 1H4-derived compounds and analysis of their mechanism of action.