Abstract
FK506-binding proteins have been implicated in numerous human diseases suggesting novel therapeutic opportunities. In particular, the large FKBP51 has emerged as an important regulator of the stress-coping system and as an established risk factor for stress-related disorders. The principal druggabilty of FKBPs is evidenced by the prototypical high affinity ligands FK506 and rapamycin but the development of more refined and selective chemical probes for FKBPs has been challenging. In this review we summarize recent advances in the development of FKBP ligands, which cumulated in the first highly selective ligands for FKBP51. The best ligand SAFit2 allowed the proof-of-concept in mice for FKBP51 inhibitors as potentially novel antidepressants. Finally, we discuss pending issues that need to be addressed for the further development of FKBP51-directed drugs.
Keywords: Antidepressants, FKBP ligand, FKBP51-directed drugs, FK506-binding proteins, homology, therapeutic.
Current Molecular Pharmacology
Title:Recent Progress in FKBP Ligand Development
Volume: 9
Author(s): Xixi Feng, Sebastian Pomplun and Felix Hausch
Affiliation:
Keywords: Antidepressants, FKBP ligand, FKBP51-directed drugs, FK506-binding proteins, homology, therapeutic.
Abstract: FK506-binding proteins have been implicated in numerous human diseases suggesting novel therapeutic opportunities. In particular, the large FKBP51 has emerged as an important regulator of the stress-coping system and as an established risk factor for stress-related disorders. The principal druggabilty of FKBPs is evidenced by the prototypical high affinity ligands FK506 and rapamycin but the development of more refined and selective chemical probes for FKBPs has been challenging. In this review we summarize recent advances in the development of FKBP ligands, which cumulated in the first highly selective ligands for FKBP51. The best ligand SAFit2 allowed the proof-of-concept in mice for FKBP51 inhibitors as potentially novel antidepressants. Finally, we discuss pending issues that need to be addressed for the further development of FKBP51-directed drugs.
Export Options
About this article
Cite this article as:
Feng Xixi, Pomplun Sebastian and Hausch Felix, Recent Progress in FKBP Ligand Development, Current Molecular Pharmacology 2016; 9 (1) . https://dx.doi.org/10.2174/1874467208666150519113313
DOI https://dx.doi.org/10.2174/1874467208666150519113313 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Epigenetics, Depression and Antidepressant Treatment
Current Pharmaceutical Design Neuroprotective Effects of Fisetin in Alzheimer’s and Parkinson’s Diseases: From Chemistry to Medicine
Current Topics in Medicinal Chemistry Monoclonal Antibodies, Small Molecule Inhibitors and Antibody-drug Conjugates as HER2 Inhibitors
Current Medicinal Chemistry Unraveling Potential Candidate Targets Associated with Expression of p16<sup>INK4a</sup> or p16 Truncated Fragment by Comparative Proteomics Analysis
Current Proteomics Neuropeptide FF Inhibits LPS-Mediated Osteoclast Differentiation of RAW264.7 Cells
Protein & Peptide Letters Passive and Active Tumour Targeting with Nanocarriers
Current Drug Discovery Technologies Therapeutic Potential of Multifunctional Tacrine Analogues
Current Neuropharmacology Endothelial Dysfunction in Metabolic Diseases: Role of Oxidation and Possible Therapeutic Employment of N-acetylcysteine
Current Medicinal Chemistry Gene Expression Analysis Approach to Establish Possible Links Between Parkinson's Disease, Cancer and Cardiovascular Diseases
CNS & Neurological Disorders - Drug Targets Dual Roles of Sulforaphane in Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Hormonal Control of the Neuropeptide Y System
Current Protein & Peptide Science CHF5074 Protects SH-SY5Y Human Neuronal-like Cells from Amyloidbeta 25-35 and Tumor Necrosis Factor Related Apoptosis Inducing Ligand Toxicity In Vitro
Current Alzheimer Research Nitrone Derivatives as Therapeutics: From Chemical Modification to Specific-targeting
Current Topics in Medicinal Chemistry A Prooxidant Mechanism for the Anticancer and Chemopreventive Properties of Plant Polyphenols
Current Drug Targets Biological Modulation by Lectins and Their Ligands in Tumor Progression and Metastasis
Anti-Cancer Agents in Medicinal Chemistry New Approaches to Target Cancer Stem Cells: Current Scenario
Mini-Reviews in Medicinal Chemistry Pleiotropic Effects of Cathepsin D
Endocrine, Metabolic & Immune Disorders - Drug Targets Subtype Selectivity in Phosphodiesterase 4 (PDE4): A Bottleneck in Rational Drug Design
Current Pharmaceutical Design Pleiotropic Effects of Cardioactive Glycosides
Current Medicinal Chemistry Nitric Oxide Releasing Nanomaterials for Cancer Treatment: Current Status and Perspectives
Current Topics in Medicinal Chemistry