FKBP12-binding domain analogues of FK506 are potent, nonimmunosuppressive neurotrophic agents in vitro and promote recovery in a mouse model of Parkinson's disease

G. S. Hamilton, W. Huang, M. A. Connolly, D. T. Ross, H. Guo, H. L. Valentine, P. D. Suzdak, J. P. Steiner

Research output: Contribution to journalArticlepeer-review

Abstract

A series of simple N-(glyoxyl)pipecolate esters were synthesized as mimics of the FKBP12- binding domain portion of FK506. Compounds which were effective inhibitors of the prolyl isomerase activity of FKBP12 were extraordinarily potent neurotrophic agents in vitro, and were effective in a mouse model of Parkinson's Disease. These results suggest that FKBP12 ligands have therapeutic utility in neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)1785-1790
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume7
Issue number13
DOIs
StatePublished - Jul 8 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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