Isoxazolyl-serine-based agonists of peroxisome proliferator-activated receptor: Design, synthesis, and effects on cardiomyocyte differentiation

Zhi Liang Wei, Pavel A. Petukhov, Fero Bizik, Joaquim Cabral Teixeira, Mark Mercola, Eugene A. Volpe, Robert I. Glazer, Timothy M. Willson, Alan P. Kozikowski

Research output: Contribution to journalArticlepeer-review

Abstract

The peroxisome proliferator-activated receptors (PPARs) are important molecular targets for the development of drugs for the treatment of human metabolic diseases, inflammation, and cancer. They are known to be activated by a variety of structurally diverse compounds. Using a structure-based drug design approach, we designed and synthesized a series of novel isoxazolyl-serine-based PPAR ligands possessing moderate affinities. Some of the new PPAR ligands were able to stimulate cardiomyocyte differentiation from murine ES cells. Ligand 1a was the most active one tested at concentrations between 1.25 to 20 μM between days 2-6, coinciding with the period when mesodermal cells can be recruited to become cardiomyocytes. Notably, the known PPARα, γ, and δ agonists tested, e.g., fenofibrate, rosiglitazone, and GW501516, were inactive in this assay.

Original languageEnglish (US)
Pages (from-to)16714-16715
Number of pages2
JournalJournal of the American Chemical Society
Volume126
Issue number51
DOIs
StatePublished - Dec 29 2004

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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