Analysis of the Selective Antagonist SAFit2 as a Chemical Probe for the FK506-Binding Protein 51

  • ACS Pharmacol Transl Sci. 2023 Feb 14;6(3):361-371. doi: 10.1021/acsptsci.2c00234.
Vanessa Buffa  1 ,  Fabian H Knaup  1 ,  Tim Heymann  1 ,  Margherita Springer  2 ,  Mathias V Schmidt  2 ,  Felix Hausch  1
Affiliations
  • 1. Department of Chemistry and Biochemistry, Clemens-Schöpf-Institute, Technical University Darmstadt, Alarich-Weiss Straße 4, 64287 Darmstadt, Germany.
  • 2. Research Group Neurobiology of Stress Resilience, Max Planck Institute of Psychiatry, 80804 Munich, Germany.
PMID: 36926456 DOI: 10.1021/acsptsci.2c00234
Abstract

The FK506-binding protein 51 (FKBP51) has emerged as an important regulator of the mammalian stress response and is involved in persistent pain states and metabolic pathways. The FK506 analog SAFit2 (short for selective antagonist of FKBP51 by induced fit) was the first potent and selective FKBP51 ligand with an acceptable pharmacokinetic profile. At present, SAFit2 represents the gold standard for FKBP51 pharmacology and has been extensively used in numerous biological studies. Here we review the current knowledge on SAFit2 as well as guidelines for its use.