PF-4800567

PF-4800567

Identifiers
IUPAC name 3-(3-chloro-phenoxymethyl)-1-(tetrahydro-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine
CAS Number	1188296-52-7
PubChem (CID)	53472153
IUPHAR/BPS	8050
ChemSpider	26325201
ChEBI	CHEBI:87237
Chemical and physical data
Formula	C17H18ClN5O2
Molar mass	359.809 g/mol
3D model (Jmol)	Interactive image
SMILES c4c(Cl)cccc4OCc(c1c3N)nn(c1ncn3)C2CCOCC2
InChI InChI=1S/C17H18ClN5O2/c18-11-2-1-3-13(8-11)25-9-14-15-16(19)20-10-21-17(15)23(22-14)12-4-6-24-7-5-12/h1-3,8,10,12H,4-7,9H2,(H2,19,20,21) Key:AUMDBEHGJRZSOO-UHFFFAOYSA-N

PF-4800567 is a drug developed by Pfizer which acts as a selective inhibitor of the enzyme Casein kinase 1 epsilon (CK1-ε), and has mainly been used in the study of the casein kinase 1 enzymes in the regulation of circadian rhythm,^[1][2] as well as showing potential neuroprotective effects.^[3] While this research has shown that circadian rhythm is modulated primarily by the alternate isoform CK1-δ rather than CK1-ε,^[4] both PF-4800567 and the related non-selective CK1-δ/ε inhibitor PF-670462 were found in animal studies to enhance responses to certain drugs of abuse such as methamphetamine and fentanyl, which suggests a role for CK1-ε in negative regulation of sensitivity to stimulant and opioid drugs.^[5][6]

References

1. Walton KM, Fisher K, Rubitski D, Marconi M, Meng QJ, Sládek M, Adams J, Bass M, Chandrasekaran R, Butler T, Griffor M, Rajamohan F, Serpa M, Chen Y, Claffey M, Hastings M, Loudon A, Maywood E, Ohren J, Doran A, Wager TT. Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period. Journal of Pharmacology and Experimental Therapeutics. 2009 Aug;330(2):430-9. PMID 19458106
2. Meng QJ, Maywood ES, Bechtold DA, Lu WQ, Li J, Gibbs JE, Dupré SM, Chesham JE, Rajamohan F, Knafels J, Sneed B, Zawadzke LE, Ohren JF, Walton KM, Wager TT, Hastings MH, Loudon AS. Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes. Proceedings of the National Academy of Sciences USA. 2010 Aug 24;107(34):15240-5. PMID 20696890
3. Perez, D. I.; Gil, C.; Martinez, A. (2011). "Protein kinases CK1 and CK2 as new targets for neurodegenerative diseases". Medicinal Research Reviews. 31 (6): 924–954. doi:10.1002/med.20207. PMID 20577972.
4. Etchegaray, J. P.; Yu, E. A.; Indic, P.; Dallmann, R.; Weaver, D. R. (2010). Yamazaki, Shin, ed. "Casein Kinase 1 Delta (CK1δ) Regulates Period Length of the Mouse Suprachiasmatic Circadian Clock in Vitro". PLoS ONE. 5 (4): e10303. doi:10.1371/journal.pone.0010303. PMC 2858662. PMID 20421981.
5. Bryant CD, Graham ME, Distler MG, Munoz MB, Li D, Vezina P, Sokoloff G, Palmer AA. A role for casein kinase 1 epsilon in the locomotor stimulant response to methamphetamine. Psychopharmacology (Berlin). 2009 May;203(4):703-11. PMID 19050854
6. Bryant, C. D.; Parker, C. C.; Zhou, L.; Olker, C.; Chandrasekaran, R. Y.; Wager, T. T.; Bolivar, V. J.; Loudon, A. S.; Vitaterna, M. H.; Turek, F. W.; Palmer, A. A. (2011). "Csnk1e is a Genetic Regulator of Sensitivity to Psychostimulants and Opioids". Neuropsychopharmacology. 37 (4): 1026–1035. doi:10.1038/npp.2011.287. PMC 3280656. PMID 22089318. PMID 22089318