WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H525952
CAS#: 1331782-27-4
Description: PF-04995274 is a 5-HT4 receptor partial agonist. It is thought to act centrally as a pro-cognitive agent that is being developed for the treatment of Alzheimer's disease (AD).
Hodoodo Cat#: H525952
Name: PF-04995274
CAS#: 1331782-27-4
Chemical Formula: C23H32N2O6
Exact Mass: 432.23
Molecular Weight: 432.520
Elemental Analysis: C, 63.87; H, 7.46; N, 6.48; O, 22.19
Synonym: PF-04995274; PF 04995274; PF04995274; PF-4995274; PF 4995274; PF4995274.
IUPAC/Chemical Name: (R)-4-((4-(((4-(Tetrahydrofuran-3-yloxy)-1,2-benzisoxazol-3-yl)oxy)methyl)piperidin-1-yl)methyl)tetrahydro-2H-pyran-4-ol
InChi Key: WLLOFQROROXOMO-GOSISDBHSA-N
InChi Code: InChI=1S/C23H32N2O6/c26-23(7-12-27-13-8-23)16-25-9-4-17(5-10-25)14-29-22-21-19(30-18-6-11-28-15-18)2-1-3-20(21)31-24-22/h1-3,17-18,26H,4-16H2/t18-/m1/s1
SMILES Code: OC1(CN2CCC(COC3=NOC4=C3C(O[C@H]5COCC5)=CC=C4)CC2)CCOCC1
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
Biological target: | PF-04995274 is a partial agonist of serotonin 4 receptor (5-HT4R) with EC50 of 0.47 nM, 0.36 nM, 0.37 nM and 0.26 nM for human 5-HT4A/4B/4D/4E, respectively. |
In vitro activity: | TBD |
In vivo activity: | Whether PF-04995274 can be prophylactic in male 129S6/SvEv mice was evaluated. Male 129S6/SvEv mice were injected with saline or PF-04995274 (3 or 10 mg/kg) (Fig. 4a). One week later, mice were administered 3-shock CFC (contextual fear conditioning). Both groups of mice exhibited comparable levels of freezing during CFC training (Fig. 4b). Five days later, mice were re-exposed to the training context. PF-04995274 at 10, but not 3 mg/kg, attenuated learned fear when compared with saline administration. Stress-induced anxiety-like behavior was next quantified. In the OF, all groups of mice traveled a comparable distance (Fig. 4h). In the EPM (elevated plus maze), all groups of mice spent comparable time in the open arms (Fig. 4i) and entered into the open arms a comparable number of times (Fig. 4j). In the NSF (novelty suppressed feeding) paradigm, all groups of mice approached the pellet in a comparable amount of time (Fig. 4k, l). Finally, all mice lost a comparable amount of weight during the NSF paradigm (Fig. 4m). In summary, these data indicate that a single injection of PF-04995274 results in prophylactic efficacy by attenuating learned fear and decreasing stress-induced depressive-like behavior. Reference: Neuropsychopharmacology. 2020 Feb;45(3):542-552. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969048/ |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
DMSO | 20.0 | 46.20 |
The following data is based on the product molecular weight 432.52 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
---|---|---|---|
1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
Formulation protocol: | 1. Chen BK, Mendez-David I, Luna VM, Faye C, Gardier AM, David DJ, Denny CA. Prophylactic efficacy of 5-HT4R agonists against stress. Neuropsychopharmacology. 2020 Feb;45(3):542-552. doi: 10.1038/s41386-019-0540-3. Epub 2019 Oct 10. PMID: 31600767; PMCID: PMC6969048. |
In vitro protocol: | TBD |
In vivo protocol: | 1. Chen BK, Mendez-David I, Luna VM, Faye C, Gardier AM, David DJ, Denny CA. Prophylactic efficacy of 5-HT4R agonists against stress. Neuropsychopharmacology. 2020 Feb;45(3):542-552. doi: 10.1038/s41386-019-0540-3. Epub 2019 Oct 10. PMID: 31600767; PMCID: PMC6969048. |
1: Nirogi R, Kandikere V, Bhyrapuneni G, Saralaya R, Ajjala DR, Aleti RR, Rasheed MA. In-vivo rat striatal 5-HT4 receptor occupancy using non-radiolabelled SB207145. J Pharm Pharmacol. 2013 May;65(5):704-12. doi: 10.1111/jphp.12030. Epub 2013 Jan 25. PubMed PMID: 23600388.