| Identification | Back Directory | [Name]
PF 04995274 | [CAS]
1331782-27-4 | [Synonyms]
PF 04995274
PF04995274;PF 04995274
PF-04995274 >=98% (HPLC)
4-[[4-[[4-[(3R)-oxolan-3-yl]oxy-1,2-benzoxazol-3-yl]oxymethyl]piperidin-1-yl]methyl]oxan-4-ol
2H-Pyran-4-ol, tetrahydro-4-[[4-[[[4-[[(3R)-tetrahydro-3-furanyl]oxy]-1,2-benzisoxazol-3-yl]oxy]methyl]-1-piperidinyl]methyl]- | [Molecular Formula]
C23H32N2O6 | [MOL File]
1331782-27-4.mol | [Molecular Weight]
432.51 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:20.0(Max Conc. mg/mL);46.2(Max Conc. mM) | [form ]
A crystalline solid | [color ]
White to off-white |
| Hazard Information | Back Directory | [Description]
PF-04995274 is a partial agonist of the serotonin (5-HT) receptor subtypes 5-HT4A, 5-HT4B, 5-HT4D, and 5-HT4E (Kis = 0.36, 0.46, 0.15, and 0.32 nM, respectively, in a radioligand binding assay). It increases cAMP levels in HEK293 cells expressing 5-HT4A, 5-HT4B, 5-HT4D, and 5-HT4E receptors (EC50s = 0.47, 0.36, 0.37, and 0.26 nM, respectively, for the human recombinant receptors). PF-04995274 decreases scopolamine-induced increases in the distance traveled in the Morris water maze in rats when administered at a dose of 0.032 mg/kg. | [Uses]
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 for cognitive disorders associated with Alzheimer's disease[1][2][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.
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| [IC 50]
5-HT4 Receptor | [References]
[1] Chen BK, et al. Prophylactic efficacy of 5-HT4R agonists against stress. Neuropsychopharmacology. 2019 Oct 10. DOI:10.1038/s41386-019-0540-3
[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). |
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BOC Sciences
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https://www.bocsci.com |
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