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https://www.selleckchem.com/products/17-DMAG,Hydrochloride-Salt.html The GPR17 receptor, expressed on oligodendroglial precursors (OPCs, the myelin producing cells), has emerged as an attractive target for a pro-myelinating strategy in multiple sclerosis (MS). However, the proof-of-concept that selective GPR17 ligands actually exert protective activity in vivo is still missing. Here, we exploited an iterative drug discovery pipeline to prioritize novel and selective GPR17 pro-myelinating agents out of more than 1,000,000 compounds. We first performed an in silico high-throughput screening on GPR17 structural model to identify three chemically-diverse ligand families that were then combinatorially exploded and refined. Top-scoring compounds were sequentially tested on reference pharmacological in vitro assays with increasing complexity, ending with myelinating OPC-neuron co-cultures. Successful ligands were filtered through in silico simulations of metabolism and pharmacokinetics, to select the most promising hits, whose dose and ability to target the central nervous system were then determined in vivo. Finally, we show that, when administered according to a preventive protocol, one of them (named by us as galinex) is able to significantly delay the onset of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. This outcome validates the predictivity of our pipeline to identify novel MS-modifying agents.OBJECTIVE This meta-analysis aimed at critically assessing currently available evidence regarding the overall effectiveness of Piezocision in accelerating orthodontic tooth movement, as well as the adverse effects of this intervention in orthodontic patients. SEARCH METHODS Electronic search of 6 databases and additional manual searches up to April 2019 without restrictions, also update the search was done by 20th November. SELECTION CRITERIA Randomized controlled trials (RCT) and controlled clinical trials (CCT) reporting piezocision-assisted orthodon

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