Piperazic acid derivatives inhibit Gli1 in Hedgehog signaling pathway

Bioorg Med Chem Lett. 2016 Sep 15;26(18):4423-4426. doi: 10.1016/j.bmcl.2016.08.008. Epub 2016 Aug 4.

Abstract

Piperazic acid, a non-proteinogenic amino acid, found in complex secondary metabolites and peptide natural substances, has shown down regulation of Gli1 expression in Hedgehog signaling pathway in cell based assays. Further structure activity relationship study indicated that amide derivatives of piperazic acid are more potent than piperazic acid itself, with little to no toxicity. However, other cellular components involved in the pathway were not affected. To the best of our knowledge, this is the first report on the inhibitory property of piperazic acid in this pathway. Hence, this molecule could serve as a useful tool for studying Hedgehog signaling.

Keywords: Gli; Hedgehog signaling; Hedgehog-inhibitors; Piperazic acid; Shh-LIGHT2 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Hedgehog Proteins / metabolism*
  • Pyridazines / pharmacology*
  • Signal Transduction / drug effects*
  • Zinc Finger Protein GLI1 / metabolism*

Substances

  • Hedgehog Proteins
  • Pyridazines
  • Zinc Finger Protein GLI1
  • piperazic acid