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Details

Stereochemistry ACHIRAL
Molecular Formula C25H20N4O.C4H6O4
Molecular Weight 510.5405
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MARDEPODECT SUCCINATE

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 C25H20N4O
Molecular Weight 392.4525
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C4H6O4
Molecular Weight 118.088
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

Targets

Primary TargetPharmacologyConditionPotency
0.37 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PubMed

PubMed

TitleDatePubMed
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
Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia.
2009 Nov
Effects of phosphodiesterase 10 inhibition on striatal cyclic AMP and peripheral physiology in rats.
2010
The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis.
2010 Nov
Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington's disease.
2010 Oct 15
Synthesis, in vivo occupancy, and radiolabeling of potent phosphodiesterase subtype-10 inhibitors as candidates for positron emission tomography imaging.
2011 Aug 25
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 Tue Oct 22 09:18:29 UTC 2019
Edited
by admin
on Tue Oct 22 09:18:29 UTC 2019
Record UNII
TJ5KAZ8T5G
Record Status Validated (UNII)
Record Version
  • Download
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
Created by admin on Tue Oct 22 09:18:29 UTC 2019 , Edited by admin on Tue Oct 22 09:18:29 UTC 2019
Code System Code Type Description
CAS
1037309-45-7
Created by admin on Tue Oct 22 09:18:29 UTC 2019 , Edited by admin on Tue Oct 22 09:18:29 UTC 2019
PRIMARY
PUBCHEM
24857794
Created by admin on Tue Oct 22 09:18:29 UTC 2019 , Edited by admin on Tue Oct 22 09:18:29 UTC 2019
PRIMARY
EPA CompTox
1037309-45-7
Created by admin on Tue Oct 22 09:18:29 UTC 2019 , Edited by admin on Tue Oct 22 09:18:29 UTC 2019
PRIMARY
EU-Orphan Drug
EU/3/16/1691(POSITIVE)
Created by admin on Tue Oct 22 09:18:29 UTC 2019 , Edited by admin on Tue Oct 22 09:18:29 UTC 2019
PRIMARY On 14 July 2016, orphan designation (EU/3/16/1691) was granted by the European Commission to Pfizer Limited, United Kingdom, for 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline succinic acid for the treatment of Huntington's disease.
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PARENT -> SALT/SOLVATE
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ACTIVE MOIETY