{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tarr JC"],"funding":["NIMH NIH HHS"],"pagination":["884-95"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3503349"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["3(11)"],"pubmed_abstract":["The M(1) muscarinic acetylcholine receptor is thought to play an important role in memory and cognition, making it a potential target for the treatment of Alzheimer's disease (AD) and schizophrenia. Moreover, M(1) interacts with BACE1 and regulates its proteosomal degradation, suggesting selective M(1) activation could afford both palliative cognitive benefit as well as disease modification in AD. A key challenge in targeting the muscarinic acetylcholine receptors is achieving mAChR subtype selectivity. Our lab has previously reported the M(1) selective positive allosteric modulator ML169. Herein we describe our efforts to further optimize this lead compound by preparing analogue libraries and probing novel scaffolds. We were able to identify several analogues that possessed submicromolar "],"journal":["ACS chemical neuroscience"],"pubmed_title":["Targeting selective activation of M(1) for the treatment of Alzheimer's disease: further chemical optimization and pharmacological characterization of the M(1) positive allosteric modulator ML169."],"pmcid":["PMC3503349"],"funding_grant_id":["R01 MH082867","U01 MH087965","R01 MH073676","U54MH084659","U01MH087965","U54 MH084659","R01MH082867","T32 MH093366"],"pubmed_authors":["Tarr JC","Conn PJ","Sheffler DJ","Turlington ML","Niswender CM","Daniels JS","Wood MR","Klein MT","Blobaum AL","Lindsley CW","Bridges TM","Pancani T","Xiang Z","Reid PR","Morrison RD","Utley TJ","Cho HP","Klar R"],"additional_accession":[]},"is_claimable":false,"name":"Targeting selective activation of M(1) for the treatment of Alzheimer's disease: further chemical optimization and pharmacological characterization of the M(1) positive allosteric modulator ML169.","description":"The M(1) muscarinic acetylcholine receptor is thought to play an important role in memory and cognition, making it a potential target for the treatment of Alzheimer's disease (AD) and schizophrenia. Moreover, M(1) interacts with BACE1 and regulates its proteosomal degradation, suggesting selective M(1) activation could afford both palliative cognitive benefit as well as disease modification in AD. A key challenge in targeting the muscarinic acetylcholine receptors is achieving mAChR subtype selectivity. Our lab has previously reported the M(1) selective positive allosteric modulator ML169. Herein we describe our efforts to further optimize this lead compound by preparing analogue libraries and probing novel scaffolds. We were able to identify several analogues that possessed submicromolar ","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Nov","modification":"2025-05-29T21:01:34.592Z","creation":"2025-05-29T21:01:34.592Z"},"accession":"S-EPMC3503349","cross_references":{"pubmed":["23173069"],"doi":["10.1021/cn300068s"]}}