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
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
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
PubMed
Patents
Sample Use Guides
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