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
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
| 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 |
DescriptionSources: http://adisinsight.springer.com/drugs/800025561 | https://www.ncbi.nlm.nih.gov/pubmed/19630403Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/19661377
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19661377 | https://www.ncbi.nlm.nih.gov/pubmed/19630403
Curator's Comment: blood-brain-barrier penetrant https://www.ncbi.nlm.nih.gov/pubmed/25450608 | https://www.ncbi.nlm.nih.gov/pubmed/21315609
Originator
Approval Year
Cmax
| Value | Dose | Co-administered | 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 |
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
| AE | Significance | Dose | Population |
|---|---|---|---|
| Blepharospasm | 1 pt Disc. AE |
30 mg single, oral (unknown) Studied dose |
healthy n = 1 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 1 Sources: |
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 |
|
| 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 |
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
Edited
Fri Dec 15 15:25:49 UTC 2023
by
admin
on
Fri Dec 15 15:25:49 UTC 2023
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| Record UNII |
R9Y8EY0G42
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Validated (UNII)
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C170150
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PF-2545920
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IC50
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ACTIVE MOIETY |
