1451993-15-9

1451993-15-9 structure

Name: VU0467154
Chemical Name: 5-amino-3,4-dimethyl-N-(4-((trifluoromethyl)sulfonyl)benzyl)thieno-[2,3-c]pyridazine-6-carboxamide
CAS Number: 1451993-15-9
Molecular Formula: C₁₇H₁₅F₃N₄O₃S₂
Molecular Weight: 444.45100
Catalog: Signaling Pathways GPCR/G Protein mAChR
Create Date: 2018-03-24 08:02:07
Modify Date: 2024-01-10 20:53:32
VU0467154 is a positive allosteric modulator of the M4 muscarinic acetylcholine receptor (mAChR), potentiating the response to ACh with pEC50s of 7.75, 6.2 and 6 for rat, human and cynomolgus monkey M4 receptor, respectively.

Name	5-amino-3,4-dimethyl-N-(4-((trifluoromethyl)sulfonyl)benzyl)thieno-[2,3-c]pyridazine-6-carboxamide
Synonyms	VU0467154 5-amino-3,4-dimethyl-N-(4-((trifluoromethyl)sulfonyl)benzyl)thieno[2,3-c]pyridazine-6-carboxamide

Description	VU0467154 is a positive allosteric modulator of the M4 muscarinic acetylcholine receptor (mAChR), potentiating the response to ACh with pEC50s of 7.75, 6.2 and 6 for rat, human and cynomolgus monkey M4 receptor, respectively.
Related Catalog	Signaling Pathways >> GPCR/G Protein >> mAChR Signaling Pathways >> Neuronal Signaling >> mAChR Research Areas >> Neurological Disease
Target	pEC50: of 7.75 (Rat M4 receptor), 6.2 (Human M4 receptor), 6 (Cynomolgus monkey M4 receptor)[1]
In Vitro	VU0467154 is a positive allosteric modulators of the M4 muscarinic acetylcholine receptor (mAChR), robustly potentiates the response to ACh with pEC50s of 7.75, 6.2 and 6 for rat, human and cynomolgus monkey (cyno) M4 receptor, respectively. VU0467154 does not potentiate the ACh response at rat and human M1, M2, M3, or M5[1].
In Vivo	VU0467154 (1-56.6 mg/kg, p.o. or i.p.) reverses amphetamine-induced hyperlocomotion in rats. VU0467154 (0.3-30 mg/kg, i.p.) reverses amphetamine- and MK-801-induced hyperlocomotion in wild-type but not M4 KO mice. VU0467154 alone also enhances the acquisition of both contextual and cue-mediated fear conditioning in wild-type mice[1].
Animal Admin	Rats[1] To determine the relationship between in vivo efficacy of VU0467154 and brain concentrations in rats, the efficacy of VU0467154 (1, 3, 10, 30, and 56.6 mg/kg, PO; n ≥ 8 per dose level) in reversing amphetamine-induced hyperlocomotion is correlated to the brain concentrations of VU0467154 in the same animals upon study completion (1.5 h postadministration). In mice, the in vivo concentration-effect relationship for VU0467154 is determined by correlating the efficacy of VU0467154 in reversing amphetamine-induced hyperlocomotion (0.3, 1, 3, 10, and 30 mg/kg, IP) to the brain concentrations of VU0467154 in the same animals upon study completion (2.5 h postadministration). Terminal unbound brain concentrations for all treatment groups are plotted versus each animal’s efficacy in reversing amphetamine-induced hyperlocomotion. Nonlinear regression analysis of the plotted data are calculated to determine the in vivo EC50 value (nM) for VU0467154 in reversing amphetamine-induced hyperlocomotion in rats using GraphPad Prism 5.0[1].
References	[1]. Bubser M, et al. Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents. ACS Chem Neurosci. 2014 Oct 15;5(10):920-42.

Molecular Formula	C₁₇H₁₅F₃N₄O₃S₂
Molecular Weight	444.45100
Exact Mass	444.05400
PSA	151.66000
LogP	5.16670
Storage condition	2-8℃

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