MARDEPODECT SUCCINATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H20N4O.C4H6O4
Molecular Weight	510.5405
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CCC(O)=O.CN1C=C(C(=N1)C2=CC=C(OCC3=NC4=CC=CC=C4C=C3)C=C2)C5=CC=NC=C5

InChI

InChIKey=AVSAEIJRBBJXNR-UHFFFAOYSA-N

InChI=1S/C25H20N4O.C4H6O4/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;5-3(6)1-2-4(7)8/h2-16H,17H2,1H3;1-2H2,(H,5,6)(H,7,8)

HIDE SMILES / InChI

Molecular Formula	C4H6O4
Molecular Weight	118.088
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C25H20N4O
Molecular Weight	392.4525
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://adisinsight.springer.com/drugs/800025561 | https://www.ncbi.nlm.nih.gov/pubmed/19630403
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19661377

PF-2545920 is an orally-active phosphodiesterase 10A (PDE10A) inhibitor originated by Pfizer, for the treatment of Huntington's disease. PF-2545920 was originally developed by Pfizer for the treatment of schizophrenia. But later clinical studies for Schizophrenia were discontinued. PF-2545920 is a potent and selective PDE10A inhibitor with IC50 of 0.37 nM, with >1000-fold selectivity over the PDE. 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphodiesterase 10A 12 Target ID: CHEMBL4409 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19630403 \| https://www.ncbi.nlm.nih.gov/pubmed/19661377	Inhibitor 8297		0.37 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Huntington's disease 24 Sources: https://clinicaltrials.gov/ct2/show/NCT02197130 http://adisinsight.springer.com/drugs/800025561	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
104 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28122201	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	PF-2545920 serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
202 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28122201	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	PF-2545920 serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
40.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28122201	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PF-2545920 serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
21.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28122201	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	PF-1001252 serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
22.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28122201	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	PF-1001252 serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
8.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28122201	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PF-1001252 serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
30 mg single, oral (unknown) Studied dose Dose: 30 mg Route: oral Route: single Dose: 30 mg Sources: https://pubmed.ncbi.nlm.nih.gov/28122201	healthy n = 1 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/28122201	Disc. AE: Blepharospasm... AEs leading to discontinuation/dose reduction: Blepharospasm (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/28122201

AEs

AE	Significance	Dose	Population
Blepharospasm	1 pt Disc. AE	30 mg single, oral (unknown) Studied dose Dose: 30 mg Route: oral Route: single Dose: 30 mg Sources: https://pubmed.ncbi.nlm.nih.gov/28122201	healthy n = 1 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/28122201

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY100636	https://www.001chemical.com/chem/search?q=DY100636
AK Scientific	0890AA	https://aksci.com/item_detail.php?cat=0890AA
AK Scientific	2642AH	https://aksci.com/item_detail.php?cat=2642AH
Achemo Scientific Limited	AC-81156	http://www.achemo.com/search/?Keyword=AC-81156
Angene	AGN-PC-0OSKJC	http://www.angenechemical.com/productshow/AGN-PC-0OSKJC.html
ApexBio Technology	A4325	https://www.apexbt.com/catalogsearch/result/?q=A4325
AstaTech	40883	http://astatechinc.com/CPSResult.php?CRNO=40883
BLD Pharm	BD764693	http://www.bldpharm.com/search/Search.html?keyword=BD764693
BOC Sciences	1037309-45-7	http://www.bocsci.com/description.asp?cas=1037309-45-7
BOC Sciences	898562-94-2	http://www.bocsci.com/description.asp?cas=898562-94-2
Cayman Chemical	18266	http://www.caymanchem.com/app/template/Product.vm/catalog/18266
Chem Scene	CS-0501	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0501
Chem Scene	CS-5987	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5987
ChemShuttle	186173	https://www.chemshuttle.com/catalogsearch/result/?q=186173
ChemShuttle	186775	https://www.chemshuttle.com/catalogsearch/result/?q=186775
Excenen	EX-A2373	http://www.excenen.com/searchresultlist.php?id=EX-A2373
Excenen	EX-A949	http://www.excenen.com/searchresultlist.php?id=EX-A949
Lab Seeker	SC-50637	http://www.labseeker.com/search.php?keywords=SC-50637&category=0
Matrix Scientific	96089	http://www.matrixscientific.com/096089.html
MedChem Express	HY-50098	https://www.medchemexpress.com/search.html?q=HY-50098A&ft=&fa=&fp=
MedChem Express	HY-50098A	https://www.medchemexpress.com/search.html?q=HY-50098A&ft=&fa=&fp=
MolPort	MolPort-023-219-202	https://www.molport.com/shop/molecule-link/MolPort-023-219-202
MolPort	MolPort-023-332-851	https://www.molport.com/shop/molecule-link/MolPort-023-332-851
MolPort	MolPort-046-418-496	https://www.molport.com/shop/molecule-link/MolPort-046-418-496
Molcore	MC100636	http://www.molcore.com/CatMC100636.html
Molnova	M11184	https://www.molnova.com/en/serch-list.html?keywords=M11184
Molnova	M16463	https://www.molnova.com/en/serch-list.html?keywords=M16463
MuseChem	I008651	https://www.musechem.com/product/I008651.html
MuseChem	M004309	https://www.musechem.com/product/M004309.html
Selleck Chemicals	S2687	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2687
ShangHai Biochempartner	BCP05602	http://www.biochempartner.com/search_BCP05602
Sigma Aldrich	PZ0351	http://www.sigmaaldrich.com/catalog/search?term=PZ0351&interface=All&N=0&mode=match%20partialmax&lang=en®ion=US&focus=product
TargetMol	T6042	https://www.targetmol.com/search?keyword=T6042
Wonderchem	WD04LW9	http://www.wonder-chem.com/search.html?text=WD04LW9
eMolecules	104708037	https://orderbb.emolecules.com/search/#?query=104708037
eMolecules	37153230	https://orderbb.emolecules.com/search/#?query=37153230
eMolecules	44467959	https://orderbb.emolecules.com/search/#?query=44467959
mcule	MCULE-8681344563	https://mcule.com/MCULE-8681344563/
mcule	MCULE-8851941021	https://mcule.com/MCULE-8851941021/

PubMed

Title	Date	PubMed
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.	2009 Aug 27	19630403
Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia.	2009 Nov	19661377
Effects of phosphodiesterase 10 inhibition on striatal cyclic AMP and peripheral physiology in rats.	2010	20407482
The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis.	2010 Nov	20967473
Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington's disease.	2010 Oct 15	20976216
Synthesis, in vivo occupancy, and radiolabeling of potent phosphodiesterase subtype-10 inhibitors as candidates for positron emission tomography imaging.	2011 Aug 25	21777010

Patents

Sample Use Guides

In Vivo Use Guide

20 mg twice a day (BID) for 26 weeks. Each 20 mg dose will be taken as 4 tablets of 5 mg. The 20mg dose will be titrated as follow: 5mg BID for 7 days, 10mg BID for 7 days, 15 mg BID for 7 days and 20 mg BID to week 26. Study drug will be provided in weekly blister cards. 5 mg twice a day (BID) for 26 weeks. Each 5 mg dose will be taken as 4 tablets: one tablet of 5 mg and 3 tablets of matching placebo. The 5mg dose will not be titrated. Study drug will be provided in weekly blister cards.

Route of Administration: Oral

In Vitro Use Guide

Pf-2545920 comparably inhibited the growth of all human colon cancer cell lines with IC 50 values ranging from 6.9 uM to 19.6 uM. Treatment of HT-29 cells with 10 uM Pf-2545920 increased the percentage of cells undergoing apoptosis to 25.9% showing positive staining for Annexin V and 31.9% for both Annexin V and PI. Treatment of HT-29 cells with 25 uM Pf-2545920 further increased the percentage of cells undergoing apoptosis with 38.2% showing positive staining for Annexin V and 31.4 % for both Annexin V and PI.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:25:49 GMT 2023` Edited by `admin` on `Fri Dec 15 15:25:49 GMT 2023`
Record UNII	TJ5KAZ8T5G
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MARDEPODECT SUCCINATE

Common Name

English

QUINOLINE, 2-((4-(1-METHYL-4-(4-PYRIDINYL)-1H-PYRAZOL-3-YL)PHENOXY)METHYL)-, BUTANEDIOATE (1:1)

Systematic Name

English

PF-2545920 SUCCINATE

Code

English

PF-02545920 SUCCINATE

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

429914