2. Academic Validation
  3. Identification of potent and selective amidobipyridyl inhibitors of protein kinase D

Identification of potent and selective amidobipyridyl inhibitors of protein kinase D

  • J Med Chem. 2010 Aug 12;53(15):5422-38. doi: 10.1021/jm100076w.
Erik L Meredith 1,  Kimberly Beattie,  Robin Burgis,  Michael Capparelli,  Joseph Chapo,  Lucian Dipietro,  Gabriel Gamber,  Istvan Enyedy,  David B Hood,  Vinayak Hosagrahara,  Charles Jewell,  Keith A Koch,  Wendy Lee,  Douglas D Lemon,  Timothy A McKinsey,  Karl Miranda,  Nikos Pagratis,  Dillon Phan,  Craig Plato,  Chang Rao,  Olga Rozhitskaya,  Nicolas Soldermann,  Clayton Springer,  Maurice van Eis,  Richard B Vega,  Wanlin Yan,  Qingming Zhu,  Lauren G Monovich
Affiliations

Affiliation

  • 1 Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139, USA. [email protected]
PMID: 20684592 DOI: 10.1021/jm100076w
Abstract

The synthesis and biological evaluation of potent and selective PKD inhibitors are described herein. The compounds described in the present study selectively inhibit PKD among Other putative HDAC kinases. The PKD inhibitors of the present study blunt phosphorylation and subsequent nuclear export of HDAC4/5 in response to diverse agonists. These compounds further establish the central role of PKD as an HDAC4/5 kinase and enhance the current understanding of cardiac myocyte signal transduction. The in vivo efficacy of a representative example compound on heart morphology is reported herein.

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