Casein Kinase 1δ/ε Inhibitor PF-5006739 Attenuates Opioid Drug-Seeking Behavior

Wager, Travis T.; Chandrasekaran, Ramalakshmi Y.; Bradley, Jenifer A.; Rubitski, David M.; Berke, H.; Mente, Scot; Butler, Todd W.; Doran, Angela C.; Chang, Cheng; Fisher, Katherine; Knafels, John D.; Liu, Shenping; Ohren, Jeffrey F.; Marconi, Michael; DeMarco, George J.; Sneed, Blossom; Walton, Kenneth G.; Horton, David B.; Rosado, Amy; Mead, Andy N.

doi:10.1021/cn500201x

Cited by 31 publications

(30 citation statements)

References 36 publications

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“…Rab-10 interacts with Melatonin receptor type 1A (P49218) which likely mediates the circadian actions of melatonin. Another protein that was found to interact with the proteins identified in the present study was Casein kinase 1 epsilon (Q9JJ76), a Ser-Thr protein kinase that acts as a key regulator of the central clock in the suprachiasmatic nucleus 69 and that is also involved in circadian regulation of gene expression 70 . Interestingly, a circadian rhythm for F has been described in humans, with the highest plasma F concentration found around midday and the lowest one in late afternoon 71 .…”

Section: Discussionmentioning

confidence: 73%

Enteric innervation combined with proteomics for the evaluation of the effects of chronic fluoride exposure on the duodenum of rats

Melo

Perles

Zanoni

et al. 2017

Sci Rep

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Ingested fluoride (F) is absorbed mainly in the small intestine, which is controlled by the Enteric Nervous System (ENS). Although important intestinal symptomatology has been described after excessive F exposure, there have been no studies reporting the effects of F on the ENS. In this study, the effects of chronic F exposure were evaluated on the duodenums of rats through proteomic and morphological analyses. Concentrations of 0, 10, or 50 ppm of F were applied to the drinking water for 30 days. Immunofluorescence techniques were performed in the myenteric plexus of the duodenum to detect HuC/D, neuronal nitric oxide (nNOS), vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), and substance P (SP). The 50 ppm F group presented a significant decrease in the density of nNOS-IR neurons. Significant morphological alterations were also observed in HUC/D-IR and nNOS-IR neurons; VIP-IR, CGRP-IR, and SP-IR varicosities for both groups (10 and 50 ppm F). Proteomic analysis of the duodenum demonstrated alterations in the expression of several proteins, especially those related to important biological processes, such as protein polymerization, which helps to explain the downregulation of many proteins upon exposure to 50 ppm of F.

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Section: Discussionmentioning

confidence: 73%

Enteric innervation combined with proteomics for the evaluation of the effects of chronic fluoride exposure on the duodenum of rats

Melo

Perles

Zanoni

et al. 2017

Sci Rep

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“…We and others previously identified a role for Csnk1e in regulating the behavioral response to multiple abused substances, including ethanol (Perreau-Lenz et al ., 2012), opioids (Bryant et al ., 2012, Wager et al ., 2014), and psychostimulants (Bryant et al ., 2009a, Bryant et al ., 2012, Palmer et al ., 2005, Zhou et al ., 2010). Here, we extended the consequences of Csnk1e deletion to include enhanced opioid-induced locomotor activity and opioid reward (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Csnk1e codes for a gene from a family of serine/threonine-selective kinases that possess diverse molecular substrates and biological functions (Cheong & Virshup, 2011), including regulation of the Wnt signaling pathway and in development and function as a clock gene in regulating circadian rhythms which are known to influence behavioral responses to substances of abuse (Parekh et al ., 2015). Non-selective pharmacological inhibition of CSNK1E and its closely related delta isoform (CSNK1D) can affect behaviors induced by multiple abused substances, including ethanol (Perreau-Lenz et al ., 2012), psychostimulants (Bryant et al ., 2009a, Zhou et al ., 2010), and opioids (Wager et al ., 2014). A recent study used pharmacological inhibition of CSNK1D/E to demonstrate attenuation of reinstatement of self-administration of the mu opioid receptor agonist fentanyl (Wager et al ., 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Non-selective pharmacological inhibition of CSNK1E and its closely related delta isoform (CSNK1D) can affect behaviors induced by multiple abused substances, including ethanol (Perreau-Lenz et al ., 2012), psychostimulants (Bryant et al ., 2009a, Zhou et al ., 2010), and opioids (Wager et al ., 2014). A recent study used pharmacological inhibition of CSNK1D/E to demonstrate attenuation of reinstatement of self-administration of the mu opioid receptor agonist fentanyl (Wager et al ., 2014). However, it is unclear whether pharmacological inhibition of CK-1 inhibits the acute rewarding/reinforcing properties of these drugs or if it has a selective role in disrupting stimulus-responsive neuronal adaptations underlying reinstatement.…”

Section: Introductionmentioning

confidence: 99%

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Casein kinase 1‐epsilon deletion increases mu opioid receptor‐dependent behaviors and binge eating1

Goldberg

Kirkpatrick

Yazdani

et al. 2017

Genes Brain and Behavior

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Genetic and pharmacological studies indicate that casein kinase-1 epsilon (Csnk1e) contributes to psychostimulant, opioid, and ethanol motivated behaviors. We previously used pharmacological inhibition to demonstrate that Csnk1e negatively regulates the locomotor stimulant properties of opioids and psychostimulants. Here, we tested the hypothesis that Csnk1e negatively regulates opioid and psychostimulant reward using genetic inhibition and the conditioned place preference assay in Csnk1e knockout mice. Similar to pharmacological inhibition, Csnk1e knockout mice showed enhanced opioid-induced locomotor activity with the mu opioid receptor agonist fentanyl (0.2 mg/kg i.p.) as well as enhanced sensitivity to low-dose fentanyl reward (0.05 mg/kg). Interestingly, female knockout mice also showed a markedly greater escalation in consumption of sweetened palatable food – a behavioral pattern consistent with binge eating that also depends on mu opioid receptor activation. No difference was observed in fentanyl analgesia in the 52.5°C hot plate assay (0–0.4 mg/kg), naloxone conditioned place aversion (4 mg/kg), or methamphetamine conditioned place preference (0–4 mg/kg). To identify molecular adaptations associated with increased drug and food behaviors in knockout mice, we completed transcriptome analysis via mRNA sequencing of the striatum. Enrichment analysis identified terms associated with myelination and axon guidance and pathway analysis identified a differentially expressed gene set predicted to be regulated by the Wnt signaling transcription factor, Tcf7l2. To summarize, Csnk1e deletion increased mu opioid receptor-dependent behaviors, supporting previous studies indicating an endogenous negative regulatory role of Csnk1e in opioid behavior.

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“…All the other reported compounds behave mainly as dual CK1δ /ε inhibitors (ICK1δ /ε). Representative examples of dual inhibitors are PF-670462 [40], PF-5006739 [41], IC261 (SU5607) [42], and a small library of thiazoles was reported by Bischof and coworkers [43].…”

Section: Small Molecule Inhibitorsmentioning

confidence: 99%

Facts and myths of selective casein kinase 1ε einhibition

2018

J. Mol. Clin. Med.

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In the scenario of drug discovery, the challenge is to fully understand and elucidate the mechanism of action to identify, with high resolution, the molecular determinant(s) targeted by the drug and responsible for its pharmacological activity. Cancer offers scientists an almost infinite arena of signaling pathways, targets and small molecules for therapeutic intervention. Among the multiple chemotherapeutic strategies to combat cancer, synthetic lethality remains underexplored. Casein kinase 1 ε (CK1ε) is a serine/threonine protein kinase that has been described as a synthetic lethal partner of the Wnt/β-catenin signaling pathway. Despite its potential as a desirable therapeutic target, only two selective inhibitors are available: PF-4800567 and GSD0054. Until the discovery of GSD0054, CK1ε inhibitors have been considered candidate drugs exclusively in psychopharmacology. In this review, we focus on three key points which we consider essential to define the scope of CK1ε as a synthetic lethal partner and its inhibitors as chemotherapeutics: the therapeutic relevance of this kinase, the scarce availability of selective inhibitors (due to the high homology with its sibling isoform CK1δ), and the constraint of existing computational tools. This paper represents the first review covering the potential of CK1ε as a druggable target for cancer treatment.

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Casein Kinase 1δ/ε Inhibitor PF-5006739 Attenuates Opioid Drug-Seeking Behavior

Cited by 31 publications

References 36 publications

Enteric innervation combined with proteomics for the evaluation of the effects of chronic fluoride exposure on the duodenum of rats

Enteric innervation combined with proteomics for the evaluation of the effects of chronic fluoride exposure on the duodenum of rats

Casein kinase 1‐epsilon deletion increases mu opioid receptor‐dependent behaviors and binge eating1

Facts and myths of selective casein kinase 1ε einhibition

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