General Description
A cell-permeable, reversible, potent and selective inhibitor of Casein Kinase (CK1) that inhibits the CK1δ (IC
50 = 0.7-1.3 μM) and CK1ε (IC
50 = 0.6-1.4 μM) isozymes. Also inhibits CK1α
1 at much higher concentrations (IC
50 = 11-21 μM). The inhibition is competitive with respect to ATP. Has only a trivial effect on p34
cdc2 and p55
fyn (IC
50s >100 μM). Blocks the phosphorylation of p53 by CK1δ and CK1ε, thereby modulating p53′s effect on the cell cycle. At low micromolar concentrations, IC261 inhibits cytokinesis causing a transient mitotic arrest.
Biological Activity
ic261 is a novel inhibitor of ck1.the p53-targeted kinases casein kinase 1delta (ck1delta) and casein kinase 1epsilon (ck1epsilon) have been reported to be involved in regulating dna repair and chromosomal segregation.
Biochem/physiol Actions
Cell permeable: yes
in vitro
previoius study found that ic261 could trigger the mitotic checkpoint control. at low micromolar concentrations, ic261 inhibited cytokinesis leading to a transient mitotic arrest. cells with active p53 arrested in the postmitotic g1 phase by blockage of entry into the s phase. cells containing non-functional p53 had postmitotic replication developing an 8n dna content. the increase of dna content was accompanied by a high amount of micronucleated and apoptotic cells. immunfluorescence images also showed that ic261 could result in centrosome amplification causing multipolar mitosis at low concentrations [1].
in vivo
animal study indicated that intrathecal injection of ic261 (0.1-1 nmol) could dose-dependently decrease mechanical allodynia and thermal hyperalgesia that were induced by carrageenan or cfa. in addition, bath-application of ic261 (1 μm) showed only marginal effects on spontaneous excitatory postsynaptic currents recorded in the substantia gelatinosa neurons of control mice. however, ic261 could decrease the frequency of sepscs in both inflammatory pain models [2].
References
1]. behrend l, et al. ic261, a specific inhibitor of the protein kinases casein kinase 1-delta and -epsilon, triggers the mitotic checkpoint and induces p53-dependent postmitotic effects. oncogene. 2000 nov 9;19(47):5303-5313.
[2] kurihara t,et al. alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (ck1) inhibitors. mol pain.2014 mar 10;10:17.
