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., et al.

BRITISH JOURNAL OF PHARMACOLOGY, cilt.171, ss.5059-5075, 2014 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 171 Konu: 22
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1111/bph.12863
  • Dergi Adı: BRITISH JOURNAL OF PHARMACOLOGY
  • Sayfa Sayısı: ss.5059-5075

Özet

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.