PF-04995274

Names

[ Name ]:
PF-04995274

[Synonym ]:
unii-xi179pg9lv
PF-04995274

Biological Activity

[Description]:

PF-04995274 is a potent, high-affinity, orally active and partial serotonin 4 receptor (5-HT4R) agonist. PF-04995274 has an EC50 range of 0.26-0.47 nM for human 5-HT4A/4B/4D/4E (Ki range of 0.15-0.46 nM), and has an EC50 range of 0.59-0.65 nM for rat 5-HT4S/4L/4E (Ki of 0.30 nM for rat 5-HT4S). PF-04995274 is brain penetrant and can be used to treat for cognitive disorders associated with Alzheimer＇s disease[1][2][3].

[Related Catalog]:

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

[Target]

5-HT4 receptor[1][2][3]

[In Vitro]

PF-04995274 has EC50 values of 0.47 nM, 0.36 nM, 0.37 nM, 0.26 nM, 0.59 nM, 0.65 nM and 0.62 nM for human 5-HT4A/4B/4D/4E and rat 5-HT4S/4L/4E, respectively. PF-04995274 has Ki values of 0.36 nM, 0.46 nM, 0.15 nM, 0.32 nM and 0.3nM for human 5-HT4A/4B/4D/4E and rat 5-HT4S, respectively[3].

[In Vivo]

PF-04995274 (3-10 mg/kg; intravenous injection; for 17 days; male 129S6/SvEv mice) treatment results in prophylactic efficacy by attenuating learned fear and decreasing stress-induced depressive-like behavior[1]. Animal Model: Male 129S6/SvEv mice (7-8 weeks) treated with contextual fear conditioning (CFC) and forced swim test (FST)[1] Dosage: 3 mg/kg, 10 mg/kg Administration: Intravenous injection; for 17 days Result: Attenuated learned fear and decreased stress-induced depressive-like behavior.

[References]

[1]. Chen BK, et al. Prophylactic efficacy of 5-HT4R agonists against stress. Neuropsychopharmacology. 2019 Oct 10.

[2]. Grimwood S, et al. Translational receptor occupancy for the 5-HT4 partial agonist PF-04995274 in rats, non-human primates and healthy volunteers. Alzheimer’s Dement: J Alzheimer’s Assoc. 2011;7:S653.

[3]. Timothy Nicholas1, et al. Systems pharmacology modeling in neuroscience: Prediction and outcome of PF-04995274, a 5-HT4 partial agonist, in a clinical scopolamine impairment trial. Advances in Alzheimer's Disease. Vol.2 No.3(2013).

Chemical & Physical Properties

[ Molecular Formula ]:
C₂₃H₃₂N₂O₆

[ Molecular Weight ]:
432.51000

[ Exact Mass ]:
432.22600

[ PSA ]:
86.42000

[ LogP ]:
2.56570

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Related Compounds

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