866933-46-2

866933-46-2 structure

Name: Velusetrag
Chemical Name: N-[8-[(2R)-2-hydroxy-3-[methyl(methylsulfonyl)amino]propyl]-8-azabicyclo[3.2.1]octan-3-yl]-2-oxo-1-propan-2-ylquinoline-3-carboxamide
CAS Number: 866933-46-2
Molecular Formula: C₂₅H₃₆N₄O₅S
Molecular Weight: 504.64200
Catalog: Signaling Pathways GPCR/G Protein 5-HT Receptor
Create Date: 2019-02-17 11:45:18
Modify Date: 2024-01-08 06:40:36
Velusetrag (TD-5108) is an orally active, potent and selective agonist of serotonin 5-HT4 receptor (5-HT4R), with a pKi of 7.7. Velusetrag exhibits no affinity (Ki>10 μM) for 5-HT2A and 5-HT2B receptors. Velusetrag can be used for the research of gastrointestinal diseases and Parkinson's disease[1][2][3][4][5].

Name	N-[8-[(2R)-2-hydroxy-3-[methyl(methylsulfonyl)amino]propyl]-8-azabicyclo[3.2.1]octan-3-yl]-2-oxo-1-propan-2-ylquinoline-3-carboxamide

Description	Velusetrag (TD-5108) is an orally active, potent and selective agonist of serotonin 5-HT4 receptor (5-HT4R), with a pKi of 7.7. Velusetrag exhibits no affinity (Ki>10 μM) for 5-HT2A and 5-HT2B receptors. Velusetrag can be used for the research of gastrointestinal diseases and Parkinson's disease[1][2][3][4][5].
Related Catalog	Research Areas >> Metabolic Disease Research Areas >> Neurological Disease Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor
Target	5-HT4 Receptor:7.7 (pKi)
In Vitro	Velusetrag (10 pM-100 μM) concentration-dependently increases the cAMP in HEK-293 cells stably transfected with the h5-HT4(c) receptor, with a pEC50 of 8.3[1]. Velusetrag (100 pM-1 μM) produces concentration-dependent contraction of the guinea pig colonic longitudinal muscle/myenteric plexus (LMMP), with a pEC50 of 7.9[1]. Velusetrag (0.001-10 μM) produces a concentration-dependent relaxation of the carbachol (3 μM)-precontracted rat esophagus, with a pEC50 of 7.9[1].
In Vivo	Velusetrag (3 mg/kg; a single i.p.) significantly improves the facilitation of contextual fear extinction in PD mice[3]. Velusetrag (3 mg/kg; a single i.p.) increases hippocampal cAMP levels in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice[3]. Velusetrag (0.003-3 mg/kg; a single s.c.) increases colonic transit in a dose-dependent manner and reduces the time taken for excretion of the dye in guinea pigs[2]. Velusetrag (0.003-1 mg/kg; a single i.v.) dose-dependently increases inter-crystal distance, consistent with relaxation of the oesophagus in rats[2]. Animal Model: Male C57BL/6 mice (7-8 weeks old) were injected with MPTP[3] Dosage: 3 mg/kg Administration: A single i.p. Result: Improved facilitation of contextual fear extinction. Did not improve the impaired rotarod performance in PD mice.
References	[1]. Smith JAM, et, al. The in vitro pharmacological profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jul;378(1):125-37. [2]. Beattie DT, et, al. The in vivo gastrointestinal activity of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jul;378(1):139-47. [3]. Ishii T, et, al. Serotonin 5-HT 4 Receptor Agonists Improve Facilitation of Contextual Fear Extinction in an MPTP-Induced Mouse Model of Parkinson's Disease. Int J Mol Sci. 2019 Oct 26;20(21):5340. [4]. Kuo B, et al. Velusetrag accelerates gastric emptying in subjects with gastroparesis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 study. Aliment Pharmacol Ther. 2021;53(10):1090-1097. [5]. Goldberg M, et al. Clinical trial: the efficacy and tolerability of velusetrag, a selective 5-HT4 agonist with high intrinsic activity, in chronic idiopathic constipation - a 4-week, randomized, double-blind, placebo-controlled, dose-response study. Aliment Pharmacol Ther. 2010;32(9):1102-1112.

Density	1.34g/cm3
Molecular Formula	C₂₅H₃₆N₄O₅S
Molecular Weight	504.64200
Exact Mass	504.24100
PSA	123.82000
LogP	3.15340

866777-83-5

866777-98-2

866933-46-2

Literature: US2008/287486 A1, ; Page/Page column 6 ;

866777-78-8

124-63-0

866933-46-2

Literature: Bioorganic and Medicinal Chemistry Letters, , vol. 22, # 19 p. 6048 - 6052

Precursor 4
866777-83-5 866777-98-2 866777-78-8 124-63-0
DownStream 0