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Recent Progress in FKBP Ligand Development.

Xixi Feng, Sebastian Pomplun, Felix Hausch1

  • 1Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany. hausch@psych.mpg.de.

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|May 20, 2015
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Summary
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FKBP51, a key regulator of stress response and risk factor for stress-related disorders, can be targeted by novel selective ligands. SAFit2 demonstrates potential for FKBP51 inhibitors as new antidepressants in preclinical models.

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Area of Science:

  • Pharmacology
  • Neuroscience
  • Molecular Biology

Background:

  • FK506-binding proteins (FKBPs) are implicated in human diseases, presenting therapeutic targets.
  • FKBP51 is a crucial regulator of the stress-coping system and a risk factor for stress-related disorders.
  • Developing selective chemical probes for FKBPs, despite known ligands like FK506, remains challenging.

Purpose of the Study:

  • To review recent advancements in the development of FKBP ligands.
  • To highlight the creation of highly selective FKBP51 ligands.
  • To discuss the potential of FKBP51 inhibitors as novel therapeutics.

Main Methods:

  • Review of recent literature on FKBP ligand development.
  • Characterization of novel selective FKBP51 ligands.
  • Preclinical proof-of-concept studies in mice.

Main Results:

  • The development of the first highly selective ligands for FKBP51 has been achieved.
  • The ligand SAFit2 demonstrated proof-of-concept for FKBP51 inhibitors as potential antidepressants in mice.
  • Recent advances offer refined chemical probes for FKBP research.

Conclusions:

  • Selective FKBP51 ligands represent a promising avenue for novel antidepressant development.
  • Further research is needed to address pending issues for FKBP51-directed drug advancement.
  • Targeting FKBP51 offers potential therapeutic opportunities for stress-related disorders.