Mardepodect free base | PDE10A inhibitor | CAS# 898562-94-2

MedKoo Cat#: 522364 | Name: Mardepodect free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Mardepodect, also known as PF-2545920, is a phosphodiesterase inhibitor selective for the PDE10A subtype, which is potentially useful for the treatment of schizophrenia. Phosphodiesterase 10A (PDE10A) is highly expressed in striatal medium spiny neurons of both the direct and indirect output pathways. PDE10A inhibitors have shown behavioral effects in rodent models that predict antipsychotic efficacy. PF-2545920 is active in a range of antipsychotic models, antagonizing apomorphine-induced climbing in mice, inhibiting conditioned avoidance responding in both rats and mice, and blocking N-methyl-D-aspartate antagonist-induced deficits in prepulse inhibition of acoustic startle response in rats, while improving baseline sensory gating in mice.

Chemical Structure

Mardepodect free base

CAS#898562-94-2 (free base)

Theoretical Analysis

MedKoo Cat#: 522364

Name: Mardepodect free base

CAS#: 898562-94-2 (free base)

Chemical Formula: C25H20N4O

Exact Mass: 392.1637

Molecular Weight: 392.46

Elemental Analysis: C, 76.51; H, 5.14; N, 14.28; O, 4.08

Price and Availability

Size	Price	Availability
25mg	USD 550.00	2 Weeks
50mg	USD 900.00	2 Weeks
100mg	USD 1,450.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

1292799-56-4 898562-94-2 (free base) 2070014-78-5 (HCl) 898563-49-0 (succinate)

Synonym

PF-2545920; PF 2545920; PF2545920; MP-10; MP10; MP 10, Mardepodect;

IUPAC/Chemical Name

2-(4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxymethyl)quinoline

InChi Key

AZEXWHKOMMASPA-UHFFFAOYSA-N

InChi Code

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

SMILES Code

CN1N=C(C2=CC=C(OCC3=NC4=CC=CC=C4C=C3)C=C2)C(C5=CC=NC=C5)=C1

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, not in water

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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Mardepodect (PF-2545920) is a potent, orally active and selective PDE10A inhibitor with an IC50 of 0.37 nM.

In vitro activity:

This study examined the PDE10A inhibitor PF-2545920 to compare its ability to promote sperm motility with that of pentoxifylline and sildenafil. PF-2545920 elevated the percentage of motile spermatozoa compared to the control, pentoxifylline, and sildenafil groups at 10 μmol l-1 (P < 0.01). It is less toxic to GC-2spd mouse spermatocytes cells and spermatozoa and causes fewer spontaneous acrosomal reactions (P < 0.05). PF-2545920 also increased mitochondrial membrane potential (P < 0.001) and altered intracellular calcium (P < 0.05) in a dose-dependent manner, including increasing sperm hyaluronic acid penetrating ability (P < 0.05). Reference: Asian J Androl. 2023 Apr 4. https://pubmed.ncbi.nlm.nih.gov/37026191/

In vivo activity:

This study examined the effect of MP-10 in neuroinflammation and PD mouse models. The anti-inflammatory effect of MP-10 was confirmed in vivo. Specifically, MP-10 inhibited microglial activation and proinflammatory gene expression in the brains of LPS-injected mice. Moreover, MP-10 rescued behavioral deficits and recovered dopaminergic neuronal cell death in the brains of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. MP-10 also reduced microglial activation in this PD mouse model. Reference: J Neuroimmune Pharmacol. 2021 Jun;16(2):470-482. https://pubmed.ncbi.nlm.nih.gov/32671618/

	Solvent	mg/mL	mM
Solubility
	DMF:PBS (pH 7.2) (1:20)	0.1	0.13
	DMSO	30.0	76.44
	Ethanol	0.5	1.27

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 392.46 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. Yang YT, Yan B, Li YH, Guo LN, Wang WW, Liu LJ, Yu HG, Diao H. Phosphodiesterase 10A inhibitor PF-2545920 as a prospective agent for the clinical promotion of sperm motility. Asian J Androl. 2023 Apr 4. doi: 10.4103/aja2022117. Epub ahead of print. PMID: 37026191. 2. Borneman RM, Gavin E, Musiyenko A, Richter W, Lee KJ, Crossman DK, Andrews JF, Wilhite AM, McClellan S, Aragon I, Ward AB, Chen X, Keeton AB, Berry K, Piazza GA, Scalici JM, da Silva LM. Phosphodiesterase 10A (PDE10A) as a novel target to suppress β-catenin and RAS signaling in epithelial ovarian cancer. J Ovarian Res. 2022 Nov 2;15(1):120. doi: 10.1186/s13048-022-01050-9. PMID: 36324187; PMCID: PMC9632086. 3. Kim DY, Park JS, Leem YH, Park JE, Kim HS. 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. 2021 Jun;16(2):470-482. doi: 10.1007/s11481-020-09943-6. Epub 2020 Jul 15. PMID: 32671618. 4. Zhang Y, Gao B, Zheng F, Lu S, Li Y, Xiong Y, Yang Q, Yang Y, Fu P, Xiao F, Wang X. The Phosphodiesterase 10A Inhibitor PF-2545920 Enhances Hippocampal Excitability and Seizure Activity Involving the Upregulation of GluA1 and NR2A in Post-synaptic Densities. Front Mol Neurosci. 2017 Apr 7;10:100. doi: 10.3389/fnmol.2017.00100. PMID: 28439226; PMCID: PMC5383654.

In vitro protocol:

In vivo protocol:

1. Kim DY, Park JS, Leem YH, Park JE, Kim HS. 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. 2021 Jun;16(2):470-482. doi: 10.1007/s11481-020-09943-6. Epub 2020 Jul 15. PMID: 32671618. 2. Zhang Y, Gao B, Zheng F, Lu S, Li Y, Xiong Y, Yang Q, Yang Y, Fu P, Xiao F, Wang X. The Phosphodiesterase 10A Inhibitor PF-2545920 Enhances Hippocampal Excitability and Seizure Activity Involving the Upregulation of GluA1 and NR2A in Post-synaptic Densities. Front Mol Neurosci. 2017 Apr 7;10:100. doi: 10.3389/fnmol.2017.00100. PMID: 28439226; PMCID: PMC5383654.

1: Hamaguchi W, Masuda N, Samizu K, Mihara T, Takama K, Watanabe T. Synthesis and in vivo evaluation of novel quinoline derivatives as phosphodiesterase 10A inhibitors. Chem Pharm Bull (Tokyo). 2014;62(12):1200-13. PubMed PMID: 25450629. 2: Lin SF, Labaree D, Chen MK, Holden D, Gallezot JD, Kapinos M, Teng JK, Najafzadeh S, Plisson C, Rabiner EA, Gunn RN, Carson RE, Huang Y. Further evaluation of [11C]MP-10 as a radiotracer for phosphodiesterase 10A: PET imaging study in rhesus monkeys and brain tissue metabolite analysis. Synapse. 2015 Feb;69(2):86-95. doi: 10.1002/syn.21792. Epub 2014 Dec 11. PubMed PMID: 25450608; PubMed Central PMCID: PMC4275380. 3: Natesan S, Ashworth S, Nielsen J, Tang SP, Salinas C, Kealey S, Lauridsen JB, Stensbøl TB, Gunn RN, Rabiner EA, Kapur S. Effect of chronic antipsychotic treatment on striatal phosphodiesterase 10A levels: a [¹¹C]MP-10 PET rodent imaging study with ex vivo confirmation. Transl Psychiatry. 2014 Apr 1;4:e376. doi: 10.1038/tp.2014.17. PubMed PMID: 24690597; PubMed Central PMCID: PMC4012281. 4: Uthayathas S, Masilamoni GJ, Shaffer CL, Schmidt CJ, Menniti FS, Papa SM. Phosphodiesterase 10A inhibitor MP-10 effects in primates: comparison with risperidone and mechanistic implications. Neuropharmacology. 2014 Feb;77:257-67. PubMed PMID: 24490227; PubMed Central PMCID: PMC3934827. 5: Bleickardt CJ, Kazdoba TM, Jones NT, Hunter JC, Hodgson RA. Antagonism of the adenosine A2A receptor attenuates akathisia-like behavior induced with MP-10 or aripiprazole in a novel non-human primate model. Pharmacol Biochem Behav. 2014 Mar;118:36-45. doi: 10.1016/j.pbb.2013.10.030. Epub 2013 Nov 8. PubMed PMID: 24211858. 6: Piccart E, Langlois X, Vanhoof G, D'Hooge R. Selective inhibition of phosphodiesterase 10A impairs appetitive and aversive conditioning and incentive salience attribution. Neuropharmacology. 2013 Dec;75:437-44. doi: 10.1016/j.neuropharm.2013.08.006. Epub 2013 Aug 22. PubMed PMID: 23973318. 7: Meslamani J, Bhajun R, Martz F, Rognan D. Computational profiling of bioactive compounds using a target-dependent composite workflow. J Chem Inf Model. 2013 Sep 23;53(9):2322-33. doi: 10.1021/ci400303n. Epub 2013 Aug 26. PubMed PMID: 23941602. 8: Hu E, Ma J, Biorn C, Lester-Zeiner D, Cho R, Rumfelt S, Kunz RK, Nixey T, Michelsen K, Miller S, Shi J, Wong J, Hill Della Puppa G, Able J, Talreja S, Hwang DR, Hitchcock SA, Porter A, Immke D, Allen JR, Treanor J, Chen H. Rapid identification of a novel small molecule phosphodiesterase 10A (PDE10A) tracer. J Med Chem. 2012 May 24;55(10):4776-87. doi: 10.1021/jm3002372. Epub 2012 May 11. PubMed PMID: 22548439. 9: Plisson C, Salinas C, Weinzimmer D, Labaree D, Lin SF, Ding YS, Jakobsen S, Smith PW, Eiji K, Carson RE, Gunn RN, Rabiner EA. Radiosynthesis and in vivo evaluation of [(11)C]MP-10 as a positron emission tomography radioligand for phosphodiesterase 10A. Nucl Med Biol. 2011 Aug;38(6):875-84. doi: 10.1016/j.nucmedbio.2011.02.005. Epub 2011 Mar 30. PubMed PMID: 21843784. 10: Dedeurwaerdere S, Wintmolders C, Vanhoof G, Langlois X. Patterns of brain glucose metabolism induced by phosphodiesterase 10A inhibitors in the mouse: a potential translational biomarker. J Pharmacol Exp Ther. 2011 Oct;339(1):210-7. doi: 10.1124/jpet.111.182766. Epub 2011 Jul 8. PubMed PMID: 21742809. 11: Tu Z, Fan J, Li S, Jones LA, Cui J, Padakanti PK, Xu J, Zeng D, Shoghi KI, Perlmutter JS, Mach RH. Radiosynthesis and in vivo evaluation of [11C]MP-10 as a PET probe for imaging PDE10A in rodent and non-human primate brain. Bioorg Med Chem. 2011 Mar 1;19(5):1666-73. doi: 10.1016/j.bmc.2011.01.032. Epub 2011 Jan 22. PubMed PMID: 21315609; PubMed Central PMCID: PMC3056285. 12: Torremans A, Ahnaou A, Van Hemelrijck A, Straetemans R, Geys H, Vanhoof G, Meert TF, Drinkenburg WH. Effects of phosphodiesterase 10 inhibition on striatal cyclic AMP and peripheral physiology in rats. Acta Neurobiol Exp (Wars). 2010;70(1):13-9. PubMed PMID: 20407482. 13: Zhang HT. Phosphodiesterase Targets for Cognitive Dysfunction and Schizophrenia--a New York Academy of Sciences Meeting. IDrugs. 2010 Mar;13(3):166-8. PubMed PMID: 20191432. 14: Grauer SM, Pulito VL, Navarra RL, Kelly MP, Kelley C, Graf R, Langen B, Logue S, Brennan J, Jiang L, Charych E, Egerland U, Liu F, Marquis KL, Malamas M, Hage T, Comery TA, Brandon NJ. Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia. J Pharmacol Exp Ther. 2009 Nov;331(2):574-90. doi: 10.1124/jpet.109.155994. Epub 2009 Aug 6. PubMed PMID: 19661377. 15: 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. 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. J Med Chem. 2009 Aug 27;52(16):5188-96. doi: 10.1021/jm900521k. PubMed PMID: 19630403.