PF-2545920

• Catalog No.: S2687
• CAS Number: 1292799-56-4
• M. F.: C25H20N4O
• M. W.: 392.4525
• Storage: -20°C

SYNONYMS

• IUPAC name: 2-{4-[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]phenoxymethyl}quinoline
• IUPAC Traditional name: 2-{4-[1-methyl-4-(pyridin-4-yl)pyrazol-3-yl]phenoxymethyl}quinoline

DATABASE IDS

• CAS Number: 1292799-56-4

PROPERTIES

• Target: PDE
• Salt Data: Free Base
• Storage Condition: -20°C

DETAILS

Description (English)

Research Area

• Description: Schizophrenia

Biological Activity

• Description: PF-2545920 is a potent and selective PDE10A inhibitor with IC50 of 0.37 nM.
• Targets: PDE10A
• IC50: 0.37 nM ^[2]
• In Vitro: MP-10 shows excellent potency and selectivity of PDE10A with IC50 of 1.26 nM. ^[1]
• In Vivo: MP-10 intraperitoneally administrated at dose of 0.3, 3, and 5 mg/kg in male CF-1 mice causes striking increases in GluR1 phosphorylation levels of 3-, 5.4-, and 4.1-fold , respectively. MP-10 at concentration of 1 μM treats Rat striatal slices for 30 min, the level of GluR1S845 phosphorylation at the cell surface is significantly increased 2-fold, without change the level of total GluR1 on the cell surface. MP-10 intraperitoneally administrated at dose of 0.3, 3, and 5 mg/kg in male CF-1 mice results in robust, statistically significant increases in CREBS133 phosphorylation of 3-, 4-, and 2.6-fold, respectively. MP-10 intraperitoneally administrated at dose of 3 mg/kg increases both enkephalin and substance-P mRNA levels in striatum of CF-1 mice. MP-10 intraperitoneally administrated at dose of 0.3–1 mg/kg decreases avoidance responding with a significant treatment effect in the mouse CAR model. Mice treated with MP-10 at dose of 0.03 mg/kg spents more time in the empty than social side in the mice, MP-10 also dose-dependently decreased locomotor activity. ^[1] PDE10A subcutaneously administrated at dose of 1 mg/kg elevates striatal cGMP about 3 fold in male CD-1 mice, while PDE10A subcutaneously administrated at dose of 3.2 mg/kg displays a maximal elevation of striatal cGMP approximately a 5-fold increase in male CD-1 mice. PDE10A intravenous injected at a dose of 0.1 mg/kg in Sprague-Dawley rats displays clearance of 36 ml/min/Kg, DE10A intravenous injected at a dose of 0.3 mg/kg in Dog Beagle displays clearance of 7.2 ml/min/Kg in vivo clearance with a moderate volume of distribution, DE10A intravenous injected at a dose of 0.03 mg/kg in Monkey Cynomolgus displays clearance of 13.9 ml/min/Kg in vivo clearance with a moderate volume of distribution. PDE10A is active with an ED50 of 1 mg/kg at a significantly lower total plasma exposure (115 nM) in the conditioned avoidance response assay (CAR) in Sprague-Dawley rats. ^[2]

References

• References: [1] Grauer SM, et al. J Pharmacol Exp Ther, 2009, 331(2), 574-590.
• References: [2] Verhoest PR, et al. J Med Chem, 2009, 52(16), 5188-5196.

REFERENCES

• Grauer SM, et al. J Pharmacol Exp Ther, 2009, 331(2), 574-590.
• Verhoest PR, et al. J Med Chem, 2009, 52(16), 5188-5196.