The chemical biology of immunophilin ligands.

  title={The chemical biology of immunophilin ligands.},
  author={S. Gaali and R. Gopalakrishnan and Y. Wang and C. Kozany and F. Hausch},
  journal={Current medicinal chemistry},
  volume={18 35},
The immunophilin ligands cyclosporin A, FK506 and rapamycin are best known for their immunosuppressive properties and their clinical use in transplantation medicine. These compounds or their analogs are also clinically used or investigated in various types of cancer, coronary angioplasty, dermatology, hepatitis C infections, and neuroprotection. Furthermore, the role of immunophilins in various pathologies is increasingly being recognized, supporting the preclinical drug development for novel… Expand
Steroid Receptor-Associated Immunophilins: Candidates for Diverse Drug-Targeting Approaches in Disease.
  • T. Ratajczak
  • Biology, Medicine
  • Current molecular pharmacology
  • 2015
This review summaries the function of these proteins as cochaperones in steroid receptor-Hsp90 complexes and elaborates on their role in alternative, Hsp90-dependent and -independent signalling pathways not involving steroid receptors. Expand
FKBPs and their role in neuronal signaling.
  • F. Hausch
  • Chemistry, Medicine
  • Biochimica et biophysica acta
  • 2015
A survey is presented on the pharmacology of neuroimmunophilin ligands, of the current understanding of individual FKBP homologs in neuronal processes and an assessment of their potential as drug targets for CNS disorders. Expand
Discovery of a new class of immunosuppressants from Trichothecium roseum co-inspired by cross-kingdom similarity in innate immunity and pharmacophore motif.
The idea that the cross-kingdom similarity in immunity among living things could provide a shorter route towards the identification of natural products valuable for the development of new immunosuppressants is strengthened. Expand
Neuroprotective effects of the immunomodulatory drug FK506 in a model of HIV1-gp120 neurotoxicity
Results suggest that FK506 might be potentially neuroprotective in patients with HAND by mitigating inflammation and mitochondrial alterations. Expand
A novel calcineurin-independent activity of cyclosporin A in Saccharomyces cerevisiae.
Fungi rely on regulatory networks to coordinate sensing of environmental stress with initiation of responses crucial for survival. Antifungal drugs are a specific type of environmental stress withExpand
Structure-Affinity Relationship Analysis of Selective FKBP51 Ligands.
A novel series of selective ligands is designed and synthesized to explore the requirements necessary for binding to the induced-fit conformation and the structure-affinity relationship provides information about beneficial structural features, which is valuable for the development of improved FKBP51-directed drugs. Expand
FKBP Ligands—Where We Are and Where to Go?
This review will give an overview of the most prominent ligands developed for FKBPs and highlight a perspective for future developments of high-affinity ligands as chemical tools and dimerizers. Expand
FK506-binding protein 12 ligands: a patent review
The interaction between FKBP12 and other receptors should be explored to guide their use as drugs in the clinical setting, and the neuroprotective mechanism of small-molecule FK BP12 ligands needs further study in order to develop them as novel drugs for treating neurological disorders. Expand
Development of NanoBRET‐Binding Assays for FKBP‐Ligand Profiling in Living Cells
The development of NanoBRET assays for the most prominent cytosolic FKBPs, FKBP12, 12.6, 51 and 52, allowed rapid profiling of FK BP ligands for target engagement and selectivity in living cells and revealed a substantial offset for the intracellular activity of these ligands compared to bicyclic ligands or natural products. Expand
Exploration of pipecolate sulfonamides as binders of the FK506-binding proteins 51 and 52.
A focused solid support-based synthesis protocol was developed, which led to ligands with submicromolar affinity for FKBP51 and FK BP52, and the molecular binding mode for one sulfonamide analogue was confirmed by X-ray crystallography. Expand