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Details

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

SHOW SMILES / InChI
Structure of MARDEPODECT

SMILES

CN1C=C(C(=N1)C2=CC=C(OCC3=NC4=CC=CC=C4C=C3)C=C2)C5=CC=NC=C5

InChI

InChIKey=AZEXWHKOMMASPA-UHFFFAOYSA-N
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

HIDE SMILES / InChI

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
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

Curator's Comment: blood-brain-barrier penetrant https://www.ncbi.nlm.nih.gov/pubmed/25450608 | https://www.ncbi.nlm.nih.gov/pubmed/21315609

Originator

Curator's Comment: # Pfizer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.37 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
104 ng/mL
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
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
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
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
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
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

Doses

DosePopulationAdverse events​
30 mg single, oral (unknown)
Studied dose
Dose: 30 mg
Route: oral
Route: single
Dose: 30 mg
Sources:
healthy
n = 1
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 1
Sources:
Disc. AE: Blepharospasm...
AEs leading to
discontinuation/dose reduction:
Blepharospasm (1 pt)
Sources:
AEs

AEs

AESignificanceDosePopulation
Blepharospasm 1 pt
Disc. AE
30 mg single, oral (unknown)
Studied dose
Dose: 30 mg
Route: oral
Route: single
Dose: 30 mg
Sources:
healthy
n = 1
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 1
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
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
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

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
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
R9Y8EY0G42
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MARDEPODECT
USAN   INN  
Official Name English
QUINOLINE, 2-((4-(1-METHYL-4-(4-PYRIDINYL)-1H-PYRAZOL-3-YL)PHENOXY)METHYL)-
Systematic Name English
Mardepodect [WHO-DD]
Common Name English
PF-02545920
Code English
MARDEPODECT [USAN]
Common Name English
MP-10
Code English
PF-2545920
Code English
mardepodect [INN]
Common Name English
Code System Code Type Description
USAN
CD-150
Created by admin on Fri Dec 15 15:25:49 GMT 2023 , Edited by admin on Fri Dec 15 15:25:49 GMT 2023
PRIMARY
INN
10509
Created by admin on Fri Dec 15 15:25:49 GMT 2023 , Edited by admin on Fri Dec 15 15:25:49 GMT 2023
PRIMARY
PUBCHEM
11581936
Created by admin on Fri Dec 15 15:25:49 GMT 2023 , Edited by admin on Fri Dec 15 15:25:49 GMT 2023
PRIMARY
CAS
898562-94-2
Created by admin on Fri Dec 15 15:25:49 GMT 2023 , Edited by admin on Fri Dec 15 15:25:49 GMT 2023
PRIMARY
DRUG BANK
DB08387
Created by admin on Fri Dec 15 15:25:49 GMT 2023 , Edited by admin on Fri Dec 15 15:25:49 GMT 2023
PRIMARY
EPA CompTox
DTXSID001025873
Created by admin on Fri Dec 15 15:25:49 GMT 2023 , Edited by admin on Fri Dec 15 15:25:49 GMT 2023
PRIMARY
SMS_ID
100000175293
Created by admin on Fri Dec 15 15:25:49 GMT 2023 , Edited by admin on Fri Dec 15 15:25:49 GMT 2023
PRIMARY
FDA UNII
R9Y8EY0G42
Created by admin on Fri Dec 15 15:25:49 GMT 2023 , Edited by admin on Fri Dec 15 15:25:49 GMT 2023
PRIMARY
NCI_THESAURUS
C170150
Created by admin on Fri Dec 15 15:25:49 GMT 2023 , Edited by admin on Fri Dec 15 15:25:49 GMT 2023
PRIMARY
WIKIPEDIA
PF-2545920
Created by admin on Fri Dec 15 15:25:49 GMT 2023 , Edited by admin on Fri Dec 15 15:25:49 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
IC50
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY