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Discovery of Monoacylglycerol Lipase (MAGL) Inhibitors Based on a Pharmacophore-Guided Virtual Screening Study
| Content Provider | MDPI |
|---|---|
| Author | Jha, Vibhu Biagi, Marzia Spinelli, Valeria Stefano, Miriana Di Macchia, Marco Minutolo, Filippo Granchi, Carlotta Poli, Giulio Tuccinardi, Tiziano |
| Copyright Year | 2020 |
| Description | Monoacylglycerol lipase (MAGL) is an important enzyme of the endocannabinoid system that catalyzes the degradation of the major endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL is associated with pathological conditions such as pain, inflammation and neurodegenerative diseases like Parkinson’s and Alzheimer’s disease. Furthermore, elevated levels of MAGL have been found in aggressive breast, ovarian and melanoma cancer cells. Due to its different potential therapeutic implications, MAGL is considered as a promising target for drug design and the discovery of novel small-molecule MAGL inhibitors is of great interest in the medicinal chemistry field. In this context, we developed a pharmacophore-based virtual screening protocol combined with molecular docking and molecular dynamics simulations, which showed a final hit rate of 50% validating the reliability of the in silico workflow and led to the identification of two promising and structurally different reversible MAGL inhibitors, VS1 and VS2. These ligands represent a valuable starting point for structure-based hit-optimization studies aimed at identifying new potent MAGL inhibitors. |
| Starting Page | 78 |
| e-ISSN | 14203049 |
| DOI | 10.3390/molecules26010078 |
| Journal | Molecules |
| Issue Number | 1 |
| Volume Number | 26 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2020-12-26 |
| Access Restriction | Open |
| Subject Keyword | Molecules Medicinal Chemistry Virtual Screening Magl Pharmacophore Model Hit Identification |
| Content Type | Text |
| Resource Type | Article |
