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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

Description

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

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
13.0 nM [IC50]
7.7 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

PubMed

Sample Use Guides

In Vivo Use Guide
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
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