PF-4800567

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]

PF-4800567
Identifiers
  • 3-(3-chloro-phenoxymethyl)-1-(tetrahydro-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC17H18ClN5O2
Molar mass359.81 g·mol−1
3D model (JSmol)
  • c4c(Cl)cccc4OCc(c1c3N)nn(c1ncn3)C2CCOCC2
  • 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

References
  1. Walton KM, Fisher K, Rubitski D, Marconi M, Meng QJ, Sládek M, et al. (August 2009). "Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period". The Journal of Pharmacology and Experimental Therapeutics. 330 (2): 430–9. doi:10.1124/jpet.109.151415. PMID 19458106. S2CID 26565986.
  2. Meng QJ, Maywood ES, Bechtold DA, Lu WQ, Li J, Gibbs JE, et al. (August 2010). "Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes". Proceedings of the National Academy of Sciences of the United States of America. 107 (34): 15240–5. Bibcode:2010PNAS..10715240M. doi:10.1073/pnas.1005101107. PMC 2930590. PMID 20696890.
  3. Perez DI, Gil C, Martinez A (November 2011). "Protein kinases CK1 and CK2 as new targets for neurodegenerative diseases". Medicinal Research Reviews. 31 (6): 924–54. doi:10.1002/med.20207. hdl:10261/87060. PMID 20577972. S2CID 206251000.
  4. Etchegaray JP, Yu EA, Indic P, Dallmann R, Weaver DR (April 2010). Yamazaki S (ed.). "Casein kinase 1 delta (CK1delta) regulates period length of the mouse suprachiasmatic circadian clock in vitro". PLOS ONE. 5 (4): e10303. Bibcode:2010PLoSO...510303E. doi:10.1371/journal.pone.0010303. PMC 2858662. PMID 20421981.
  5. Bryant CD, Graham ME, Distler MG, Munoz MB, Li D, Vezina P, et al. (May 2009). "A role for casein kinase 1 epsilon in the locomotor stimulant response to methamphetamine". Psychopharmacology. 203 (4): 703–11. doi:10.1007/s00213-008-1417-z. PMC 2729782. PMID 19050854.
  6. Bryant CD, Parker CC, Zhou L, Olker C, Chandrasekaran RY, Wager TT, et al. (March 2012). "Csnk1e is a genetic regulator of sensitivity to psychostimulants and opioids". Neuropsychopharmacology. 37 (4): 1026–35. doi:10.1038/npp.2011.287. PMC 3280656. PMID 22089318.
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