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
-
An Insight into Purine, Tyrosine and Tryptophan Derived Marine Antineoplastic Alkaloids
Anti-Cancer Agents in Medicinal Chemistry The Mechanism of Memory Impairment Induced by Aβ Chronic Administration Involves Imbalance between Cytokines and Neurotrophins in the Rat Hippocampus
Current Alzheimer Research Carbon Nanotubes in the Diagnosis and Treatment of Malignant Melanoma
Anti-Cancer Agents in Medicinal Chemistry MicroRNAs in Neuroblastoma: Biomarkers with Therapeutic Potential
Current Medicinal Chemistry Inhibition of Apoptosis in Pediatric Cancer by Survivin
Current Pediatric Reviews Pharmacological Profile and Pharmacogenomics of Anti-Cancer Drugs Used for Targeted Therapy
Current Cancer Drug Targets Neuroblastoma and Stem Cell Therapy: An Updated Review
CNS & Neurological Disorders - Drug Targets Dopamine D1 Receptors, Regulation of Gene Expression in the Brain, and Neurodegeneration
CNS & Neurological Disorders - Drug Targets Therapeutic Use of Agonists of the Nuclear Receptor PPARγ in Alzheimers Disease
Current Alzheimer Research Anti-Tumor Monoclonal Antibodies in Conjunction with β-Glucans: A Novel Anti- Cancer Immunotherapy
Current Medicinal Chemistry Engagement of Renin-Angiotensin System in Prostate Cancer
Current Cancer Drug Targets Adult Stem Cells and Biocompatible Scaffolds as Smart Drug Delivery Tools for Cardiac Tissue Repair
Current Medicinal Chemistry Targeting Tumor Ubiquitin-Proteasome Pathway with Polyphenols for Chemosensitization
Anti-Cancer Agents in Medicinal Chemistry Nampt/Visfatin/PBEF: A Functionally Multi-faceted Protein with a Pivotal Role in Malignant Tumors
Current Pharmaceutical Design Marine Derived Anticancer Drugs Targeting Microtubule
Recent Patents on Anti-Cancer Drug Discovery Physiology and Pathophysiology of Na+/H+ Exchange Isoform 1 in the Central Nervous System
Current Neurovascular Research Role of miRNAs in Cancer Diagnostics and Therapy: A Recent Update
Current Pharmaceutical Design Low Doses Naltrexone: The Potential Benefit Effects for its Use in Patients with Cancer
Current Drug Research Reviews Molecular Mechanisms of Thiamine Utilization.
Current Molecular Medicine Recent Advances in Molecular Image-Guided Cancer Radionuclide Therapy
Current Drug Targets