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Details

Stereochemistry ACHIRAL
Molecular Formula C19H20FN5.2ClH
Molecular Weight 410.316
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PF-670462

SMILES

Cl.Cl.NC1=NC=CC(=N1)C2=C(N=CN2C3CCCCC3)C4=CC=C(F)C=C4

InChI

InChIKey=PSNKGVAXBSAHCH-UHFFFAOYSA-N
InChI=1S/C19H20FN5.2ClH/c20-14-8-6-13(7-9-14)17-18(16-10-11-22-19(21)24-16)25(12-23-17)15-4-2-1-3-5-15;;/h6-12,15H,1-5H2,(H2,21,22,24);2*1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C19H20FN5
Molecular Weight 337.394
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

PF-670462 is a selective inhibitor of the δ- and ε-isoforms of casein kinase I, with IC50 values of 7.7 and 14 nM respectively, and >30 selectivity relative to 42 other kinases tested. Casein kinase Iε phosphorylates PER proteins, which are involved in setting the period of the circadian pacemaker or clock. PF-670462 is potent (IC50 7.7 nM) and effective in vivo (i.e. it induces profound phase delays in circadian periodicity). PF-670462 has being shown to have an ability to induce phase delays in circadian rhythms in rats, in which it is rapidly metabolized, and in monkeys. A potential pharmacological use of the compounds like PF-670462 could be for therapy of cognitive deficits in shift workers, mood changes in bipolar disorders, and phase advances in the sleep–wake cycle in elderly people. It has also being shown that Inhibition of the casein-kinase-1-ε/δ/ with PF-670462 prevents relapse-like alcohol drinking in rats, suggesting that CK1 inhibitors may be candidates for drug treatment development for alcoholism.

CNS Activity

Originator

Curator's Comment: # Pfizer

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Acute inhibition of casein kinase 1δ/ε rapidly delays peripheral clock gene rhythms.
2015-01
Inhibition of the casein-kinase-1-ε/δ/ prevents relapse-like alcohol drinking.
2012-08
Protein kinases CK1 and CK2 as new targets for neurodegenerative diseases.
2011-11
Chronic treatment with a selective inhibitor of casein kinase I delta/epsilon yields cumulative phase delays in circadian rhythms.
2010-07
Inhibition of casein kinase I epsilon/delta produces phase shifts in the circadian rhythms of Cynomolgus monkeys.
2009-07
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Can also be used i.p: Intraperitoneal PF-670462 (20-40 mg/kg) attenuated the locomotor stimulant response to MA (2 mg/kg) in mice https://www.ncbi.nlm.nih.gov/pubmed/19050854
Rats: Gross motor activity was used to estimate the circadian rhythms of rats maintained under a 12 L:12 D cycle. PF-670462, 10 or 30 mg/kg/day s.c., was administered once daily for 20 days either at ZT6 or ZT11 (i.e., 6 or 11 h after light onset).
Route of Administration: Other
In Vitro Use Guide
Curator's Comment: Primary lung fibroblast cells obtained from WT, Ck1ε tau mutant, and Ck1ε −/− mice bred on a PER2::Luc reporter background were used.
Treatment with PF-670462 caused significant dose-dependent lengthening of the circadian period: high-dose PF-670462 (1 uM) extended the period in WT fibroblasts to 33 h
Substance Class Chemical
Created
by admin
on Mon Mar 31 22:53:35 GMT 2025
Edited
by admin
on Mon Mar 31 22:53:35 GMT 2025
Record UNII
D68ANS5I8B
Record Status Validated (UNII)
Record Version
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Name Type Language
2-Pyrimidinamine, 4-[1-cyclohexyl-4-(4-fluorophenyl)-1H-imidazol-5-yl]-, hydrochloride (1:2)
Preferred Name English
PF-670462
Code English
Code System Code Type Description
FDA UNII
D68ANS5I8B
Created by admin on Mon Mar 31 22:53:35 GMT 2025 , Edited by admin on Mon Mar 31 22:53:35 GMT 2025
PRIMARY
EPA CompTox
DTXSID50679609
Created by admin on Mon Mar 31 22:53:35 GMT 2025 , Edited by admin on Mon Mar 31 22:53:35 GMT 2025
PRIMARY
PUBCHEM
51049607
Created by admin on Mon Mar 31 22:53:35 GMT 2025 , Edited by admin on Mon Mar 31 22:53:35 GMT 2025
PRIMARY
CAS
950912-80-8
Created by admin on Mon Mar 31 22:53:35 GMT 2025 , Edited by admin on Mon Mar 31 22:53:35 GMT 2025
PRIMARY
Related Record Type Details
ACTIVE MOIETY