FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2026049763> ?p ?o ?g. }

• W2026049763 abstract "Alzheimer's disease is the most common cause of dementia. 5-HT 4 receptors have a discrete localization in the CNS, mainly in the frontal cortex and hippocampus. 5-HT 4 receptor partial agonists may be of benefit for both the symptomatic and disease-modifying treatment of cognitive disorders via modulation of amyloid precursor protein (APP) derived peptides, amyloid beta (Aβ) and soluble amyloid precursor protein alpha (sAPPα) in the CNS. Our effective lead optimization has resulted into SUVN-D1108121 as a lead like molecule from our CNS discovery programme, exhibited pro-cognitive properties in preclinical animal models and increased neurotransmitters involved in cognition. The fuctional activity of the SUVN-D1108121 was tested in adenylyl cyclase assay in CHO cells expressing human 5-HT 4(e) receptor and Ki value was determined at novascreen in radioligand binding study using 5-HT 4 membrane. In-vitro metabolism studies (metabolic stability, CYP inhibition and protein binding), pharmacokinetic and brain penetration profile were evaluated in the preclinical species.In-vivo striatal 5-HT 4 receptor occupancy was measured in rats using LC-MS/MS based tracer analysis. Modulation of cortical sAPPα in mice and CSF amyloid- β protein levels in rats were evaluated. SUVN-1108121 exhibited partial agonist activity with an EC 50 value of 0.09 nM when tested for functional activity in adenylyl cyclase assay and Ki value of 0.15 nM in radioligand binding studies. SUVN-D1108121 is found to be stable in human in-vitro liver preparations with no drug interaction potential.SUVN-D1108121 had good oral bioavailability and efficiently penetrate the CNS with good free concentrations at the target site. SUVN-D1108121 showed dose dependent increase in striatal receptor occupancy at tested dose levels. A significant increase in the cortical sAPPα levels was observed i.e. 39, 41, 46 & 66 % at 0.3, 1, 3 and 10 mg/kg, s.c. respectively. A dose dependent decrease in CSF amyloid-β protein levels was observed in non-transgenic animal model. The preclinical data suggests that SUVN-D1108121 is a novel potent, selective, orally bioavailable and efficacious 5-HT 4 receptor partial agonist that holds promise for the management of hallmark symptomatologies observed in Alzheimer's disease. The compound is currently under further investigations to qualify as a clinical candidate." @default.
• W2026049763 created "2016-06-24" @default.
• W2026049763 creator A5000976974 @default.
• W2026049763 creator A5023454239 @default.
• W2026049763 creator A5023539276 @default.
• W2026049763 creator A5038669019 @default.
• W2026049763 creator A5042819643 @default.
• W2026049763 creator A5048506699 @default.
• W2026049763 creator A5050284513 @default.
• W2026049763 creator A5056638040 @default.
• W2026049763 creator A5058105227 @default.
• W2026049763 creator A5064727180 @default.
• W2026049763 creator A5081216144 @default.
• W2026049763 creator A5082227355 @default.
• W2026049763 creator A5084599164 @default.
• W2026049763 creator A5091732946 @default.
• W2026049763 date "2012-07-01" @default.
• W2026049763 modified "2023-09-27" @default.
• W2026049763 title "P4-221: SUVN-D1108121: A potent and selective 5-HT4 receptor partial agonist, potential drug for the treatment of Alzheimer's disease" @default.
• W2026049763 doi "https://doi.org/10.1016/j.jalz.2012.05.1926" @default.
• W2026049763 hasPublicationYear "2012" @default.
• W2026049763 type Work @default.
• W2026049763 sameAs 2026049763 @default.
• W2026049763 citedByCount "0" @default.
• W2026049763 crossrefType "journal-article" @default.
• W2026049763 hasAuthorship W2026049763A5000976974 @default.
• W2026049763 hasAuthorship W2026049763A5023454239 @default.
• W2026049763 hasAuthorship W2026049763A5023539276 @default.
• W2026049763 hasAuthorship W2026049763A5038669019 @default.
• W2026049763 hasAuthorship W2026049763A5042819643 @default.
• W2026049763 hasAuthorship W2026049763A5048506699 @default.
• W2026049763 hasAuthorship W2026049763A5050284513 @default.
• W2026049763 hasAuthorship W2026049763A5056638040 @default.
• W2026049763 hasAuthorship W2026049763A5058105227 @default.
• W2026049763 hasAuthorship W2026049763A5064727180 @default.
• W2026049763 hasAuthorship W2026049763A5081216144 @default.
• W2026049763 hasAuthorship W2026049763A5082227355 @default.
• W2026049763 hasAuthorship W2026049763A5084599164 @default.
• W2026049763 hasAuthorship W2026049763A5091732946 @default.
• W2026049763 hasConcept C126322002 @default.
• W2026049763 hasConcept C134018914 @default.
• W2026049763 hasConcept C150903083 @default.
• W2026049763 hasConcept C170493617 @default.
• W2026049763 hasConcept C185592680 @default.
• W2026049763 hasConcept C207001950 @default.
• W2026049763 hasConcept C2778938600 @default.
• W2026049763 hasConcept C2779134260 @default.
• W2026049763 hasConcept C2779178603 @default.
• W2026049763 hasConcept C31705614 @default.
• W2026049763 hasConcept C502032728 @default.
• W2026049763 hasConcept C55493867 @default.
• W2026049763 hasConcept C58732023 @default.
• W2026049763 hasConcept C67847695 @default.
• W2026049763 hasConcept C71924100 @default.
• W2026049763 hasConcept C86803240 @default.
• W2026049763 hasConcept C98274493 @default.
• W2026049763 hasConceptScore W2026049763C126322002 @default.
• W2026049763 hasConceptScore W2026049763C134018914 @default.
• W2026049763 hasConceptScore W2026049763C150903083 @default.
• W2026049763 hasConceptScore W2026049763C170493617 @default.
• W2026049763 hasConceptScore W2026049763C185592680 @default.
• W2026049763 hasConceptScore W2026049763C207001950 @default.
• W2026049763 hasConceptScore W2026049763C2778938600 @default.
• W2026049763 hasConceptScore W2026049763C2779134260 @default.
• W2026049763 hasConceptScore W2026049763C2779178603 @default.
• W2026049763 hasConceptScore W2026049763C31705614 @default.
• W2026049763 hasConceptScore W2026049763C502032728 @default.
• W2026049763 hasConceptScore W2026049763C55493867 @default.
• W2026049763 hasConceptScore W2026049763C58732023 @default.
• W2026049763 hasConceptScore W2026049763C67847695 @default.
• W2026049763 hasConceptScore W2026049763C71924100 @default.
• W2026049763 hasConceptScore W2026049763C86803240 @default.
• W2026049763 hasConceptScore W2026049763C98274493 @default.
• W2026049763 hasIssue "4S_Part_19" @default.
• W2026049763 hasLocation W20260497631 @default.
• W2026049763 hasOpenAccess W2026049763 @default.
• W2026049763 hasPrimaryLocation W20260497631 @default.
• W2026049763 hasRelatedWork W1986238933 @default.
• W2026049763 hasRelatedWork W2021687069 @default.
• W2026049763 hasRelatedWork W2027913950 @default.
• W2026049763 hasRelatedWork W2034583712 @default.
• W2026049763 hasRelatedWork W2045849221 @default.
• W2026049763 hasRelatedWork W2046298256 @default.
• W2026049763 hasRelatedWork W2050423574 @default.
• W2026049763 hasRelatedWork W2057548484 @default.
• W2026049763 hasRelatedWork W2063619316 @default.
• W2026049763 hasRelatedWork W2328651641 @default.
• W2026049763 hasVolume "8" @default.
• W2026049763 isParatext "false" @default.
• W2026049763 isRetracted "false" @default.
• W2026049763 magId "2026049763" @default.
• W2026049763 workType "article" @default.