Mardepodect (PF-2545920)

製品コードS2687 バッチS268705

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H20N4O
分子量 392.45 CAS No. 1292799-56-4
Solubility (25°C)* 体外 DMSO 100 mg/mL warmed with 50ºC water bath (254.8 mM)
Ethanol 100 mg/mL (254.8 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Mardepodect (PF-2545920) 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. [1]
in vivo PF-2545920 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]

プロトコル(参考用のみ)

キナーゼアッセイ PDE10 enzyme assay
PDE10A is generated from the full-length recombinant rat clone transfected into Sf9 cells. The enzyme is extracted from cell pellets in lysis buffer (20 mM Tris, 2 mM benzamidine, 1.0 mM Na2EDTA, 0.25 M sucrose, 100 μM PMSF, pH 7.5 at room temperature) and stored frozen at -80 °C. PDE activity is measured using a plate based Scintillation Proximity Assay (SPA) modified from an Amersham Biosciences protocol. The Km of the PDE10A preparation is experimentally determined to be 24 nM at room temperature. For competitive enzyme inhibition assays, the substrate [3H]cAMP concentration is held at 20 nM for conditions to be at or below the Km of the enzyme. The concentration of enzyme is adjusted to convert less than 10% of available substrate to end product during the assay. PF-2545920 is initially dissolved in DMSO and diluted such that the final DMSO assay concentration is 3%. Following the addition of the test agents and [3H]-cAMP, enzyme is added in buffer containing 50 mM Tris and 1.3 mM MgCl2 (pH 7.5) to a final volume of 50 ul. The incubation is allowed to proceed for 30 min at room temperature before the addition of 20 ul of PDE SPA beads at 0.2 mg/well to stop the reaction. Plates are allowed to stand 10 to 12 hours before counting in a Trilux plate reader. IC50s are calculated after the subtraction of background as determined by addition of 10 uM papaverine.
動物実験 動物モデル Jugular vein-cannulated male Sprague-Dawley rats
投薬量 0.1 mg/kg
投与方法 Inject intravenous through jugular vein catheter in a single dose 4 hours before feed

カスタマーフィードバック

Data from [Oncogene, 2014, 10.1038/onc.2014.94]

Data from [Oncogene, 2014, 10.1038/onc.2014.94]

Data from [Data independently produced by , , Am J Hum Genet, 2017, 100(1):5-20]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Phosphodiesterase 10A (PDE10A) as a novel target to suppress β-catenin and RAS signaling in epithelial ovarian cancer [ J Ovarian Res, 2022, 15(1):120] PubMed: 36324187
The Potent PDE10A Inhibitor MP-10 (PF-2545920) Suppresses Microglial Activation in LPS-Induced Neuroinflammation and MPTP-Induced Parkinson's Disease Mouse Models [ J Neuroimmune Pharmacol, 2020, 10.1007/s11481-020-09943-6] PubMed: 32671618
Proteome-scale investigation of protein allosteric regulation perturbed by somatic mutations in 7,000 cancer genomes [Shen Q Am J Hum Genet, 2017, 100(1):5-20] PubMed: 27939638
Phosphodiesterase 10A is overexpressed in lung tumor cells and inhibitors selectively suppress growth by blocking β-catenin and MAPK signaling. [ Oncotarget, 2017, 8(41):69264-69280] PubMed: 29050202
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, et al. Front Mol Neurosci, 2017, 10:100] PubMed: 28439226
A novel thermoregulatory role for PDE10A in mouse and human adipocytes. [ EMBO Mol Med, 2016, 8(7):796-812] PubMed: 27247380
Luteinizing Hormone Causes Phosphorylation and Activation of the cGMP Phosphodiesterase PDE5 in Rat Ovarian Follicles, Contributing, Together with PDE1 Activity, to the Resumption of Meiosis [Egbert JR, et al. Biol Reprod, 2016, 94(5):110] PubMed: 27009040
Phosphodiesterase 10A: a novel target for selective inhibition of colon tumor cell growth and β-catenin-dependent TCF transcriptional activity. [Li N, et al. Oncogene, 2014, 10.1038/onc.2014.94] PubMed: 24704829

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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