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Nerve growth factor inhibitor with novel-binding domain demonstrates nanomolar efficacy in both cell-based and cell-free assay systems.
- Source :
-
Pharmacology research & perspectives [Pharmacol Res Perspect] 2017 Oct; Vol. 5 (5). - Publication Year :
- 2017
-
Abstract
- Nerve growth factor (NGF), a member of the neurotrophin family, is known to regulate the development and survival of a select population of neurons through the binding and activation of the TrkA receptor. Elevated levels of NGF have been associated with painful pathologies such as diabetic neuropathy and fibromyalgia. However, completely inhibiting the NGF signal could hold significant side effects, such as those observed in a genetic condition called congenital insensitivity to pain and anhidrosis (CIPA). Previous methods of screening for NGF-inhibitors used labeling techniques which have the potential to alter molecular interactions. SPR spectroscopy and NGF-dependent cellular assays were utilized to identify a novel NGF-inhibitor, BVNP-0197 (IC <subscript>50</subscript>  = 90 nmol/L), the first NGF-inhibitor described with a high nanomolar NGF inhibition efficiency. The present study utilizes molecular modeling flexible docking to identify a novel binding domain in the loop II/IV cleft of NGF.<br /> (© 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)
- Subjects :
- Animals
Binding Sites
Cell Differentiation drug effects
Cell Line
Cell-Free System
Mice
Models, Molecular
Molecular Docking Simulation
Molecular Structure
Naphthalimides chemistry
Nerve Growth Factor antagonists & inhibitors
Phosphorylation
Rats
Naphthalimides chemical synthesis
Naphthalimides pharmacology
Nerve Growth Factor chemistry
Receptor, trkA metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2052-1707
- Volume :
- 5
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Pharmacology research & perspectives
- Publication Type :
- Academic Journal
- Accession number :
- 28971611
- Full Text :
- https://doi.org/10.1002/prp2.339