PF-2545920

Appearance:Solid powder
Purity: > 98%

Cat No:	I005378
Cas No:	898562-94-2
Product-Name:	PF-2545920
IUPAC Name:	2-[[4-(1-methyl-4-pyridin-4-ylpyrazol-3-yl)phenoxy]methyl]quinoline
InChI:	InChI=1S/C25H20N4O/c1-29-16-23(18-12-14-26-15-13-18)25(28-29)20-7-10-22(11-8-20)30-17-21-9-6-19-4-2-3-5-24(19)27-21/h2-16H,17H2,1H3
InChIKey:	AZEXWHKOMMASPA-UHFFFAOYSA-N
SMILES:	CN1C=C(C(=N1)C2=CC=C(C=C2)OCC3=NC4=CC=CC=C4C=C3)C5=CC=NC=C5

PF-2545920 (CAS 898562-94-2) is a potent and selective PDE10A inhibitor with IC50 of 0.37 nM, with >1000-fold selectivity over the PDE.

 

In vitro: PF-2545920 shows excellent potency and selectivity of PDE10A with IC50 of 1.26 nM.

In vivo: The PDE10A enzyme is expressed primarily in the brain, mostly in the striatum, nucleus accumbens and olfactory tubercle, and is thought to be particularly important in regulating the activity of dopamine-sensitive medium spiny neurons in the striatum which are known to be targets of conventional antipsychotic agents. n the conditioned avoidance response assay (CAR), PF-2545920 was active with an ED50 of 1 mg/kg. Administration of PF-2545920 to mice caused a dose dependent increase in striatal cGMP.

1:The Phosphodiesterase 10A Inhibitor PF-2545920 Enhances Hippocampal Excitability and Seizure Activity Involving the Upregulation of GluA1 and NR2A in Post-synaptic Densities. Zhang Y, Gao B, Zheng F, Lu S, Li Y, Xiong Y, Yang Q, Yang Y, Fu P, Xiao F, Wang X.Front Mol Neurosci. 2017 Apr 7;10:100. doi: 10.3389/fnmol.2017.00100. eCollection 2017. PMID: 28439226 Free PMC Article
2:Phosphodiesterase 10A inhibitor, MP-10 (PF-2545920), produces greater induction of c-Fos in dopamine D2 neurons than in D1 neurons in the neostriatum. Wilson JM, Ogden AM, Loomis S, Gilmour G, Baucum AJ 2nd, Belecky-Adams TL, Merchant KM.Neuropharmacology. 2015 Dec;99:379-86. doi: 10.1016/j.neuropharm.2015.08.008. Epub 2015 Aug 7. PMID: 26256420
3:Discovery of a novel class of phosphodiesterase 10A inhibitors and identification of clinical candidate 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the treatment of schizophrenia. Verhoest PR, Chapin DS, Corman M, Fonseca K, Harms JF, Hou X, Marr ES, Menniti FS, Nelson F, O/'Connor R, Pandit J, Proulx-Lafrance C, Schmidt AW, Schmidt CJ, Suiciak JA, Liras S.J Med Chem. 2009 Aug 27;52(16):5188-96. doi: 10.1021/jm900521k. PMID: 19630403