Casein Kinase 1δ Inhibitors as Promising Therapeutic Agents for
Neurodegenerative Disorders

Daniela      Catarzi; Flavia      Varano; Erica      Vigiani; Catia      Lambertucci; Andrea      Spinaci; Rosaria      Volpini; Vittoria      Colotta
Abstract

Casein kinase 1 (CK1) belongs to the serine-threonine kinase family and is expressed in all eukaryotic organisms. At least six human isoforms of CK1 (termed α, γ1-3, δ and ε) have been cloned and characterized. CK1δ isoform modulates several physiological processes, including DNA damage repair, circadian rhythm, cellular proliferation and apoptosis. Therefore, CK1δ dysfunction may trigger diverse pathologies, such as cancer, inflammation and central nervous system disorders. Overexpression and aberrant activity of CK1δ have been connected to hyperphosphorylation of key proteins implicated in the development of neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases and Amyotrophic Lateral Sclerosis. Thus, CK1δ inhibitors have attracted attention as potential drugs for these pathologies and several compounds have been synthesized or isolated from natural sources to be evaluated for their CK1δ inhibitory activity. Here we report a comprehensive review on the development of CK1δ inhibitors, with a particular emphasis on structure-activity relationships and computational studies, which provide useful insight for the design of novel inhibitors.
Keywords: Casein kinase 1 delta, casein kinase 1 delta inhibitors, neuroprotective agents, anticancer agents, small molecules, natural inhibitors, drug design.
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[1] 
Xu, P.; Ianes, C.; Gärtner, F.; Liu, C.; Burster, T.; Bakulev, V.; Rachidi, N.; Knippschild, U.; Bischof, J. Structure, regulation, and (patho-)physiological functions of the stress-induced protein kinase CK1 delta (CSNK1D). Gene,  2019, 715, 144005.
[http://dx.doi.org/10.1016/j.gene.2019.144005] [PMID: 31376410] 
[2] 
Pinna, L.A.; Baggio, B.; Moret, V.; Siliprandi, N. Isolation and properties of a protein kinase from rat liver microsomes. Biochim. Biophys. Acta,  1969, 178(1), 199-201.
[http://dx.doi.org/10.1016/0005-2744(69)90152-1] [PMID: 5773455] 
[3] 
Lasa, M.; Marin, O.; Pinna, L.A. Rat liver Golgi apparatus contains a protein kinase similar to the casein kinase of lactating mammary gland. Eur. J. Biochem.,  1997, 243(3), 719-725.
[http://dx.doi.org/10.1111/j.1432-1033.1997.00719.x] [PMID: 9057837] 
[4] 
Pinna, L.A. Casein kinase 2: An ‘eminence grise’ in cellular regulation? Biochim. Biophys. Acta,  1990, 1054(3), 267-284.
[http://dx.doi.org/10.1016/0167-4889(90)90098-X] [PMID: 2207178] 
[5] 
Rowles, J.; Slaughter, C.; Moomaw, C.; Hsu, J.; Cobb, M.H. Purification of casein kinase I and isolation of cDNAs encoding multiple casein kinase I-like enzymes. Proc. Natl. Acad. Sci. USA,  1991, 88(21), 9548-9552.
[http://dx.doi.org/10.1073/pnas.88.21.9548] [PMID: 1946367] 
[6] 
Zhai, L.; Graves, P.R.; Robinson, L.C.; Italiano, M.; Culbertson, M.R.; Rowles, J.; Cobb, M.H.; DePaoli-Roach, A.A.; Roach, P.J. Casein kinase I γ subfamily. Molecular cloning, expression, and characterization of three mammalian isoforms and complementation of defects in the Saccharomyces cerevisiae YCK genes. J. Biol. Chem.,  1995, 270(21), 12717-12724.
[http://dx.doi.org/10.1074/jbc.270.21.12717] [PMID: 7759525] 
[7] 
Zhang, J.; Gross, S.D.; Schroeder, M.D.; Anderson, R.A. Casein kinase I α and α L: alternative splicing-generated kinases exhibit different catalytic properties. Biochemistry,  1996, 35(50), 16319-16327.
[http://dx.doi.org/10.1021/bi9614444] [PMID: 8973207] 
[8] 
Graves, P.R.; Haas, D.W.; Hagedorn, C.H.; DePaoli-Roach, A.A.; Roach, P.J. Molecular cloning, expression, and characterization of a 49-kilodalton casein kinase I isoform from rat testis. J. Biol. Chem.,  1993, 268(9), 6394-6401.
[http://dx.doi.org/10.1016/S0021-9258(18)53265-8] [PMID: 8454611] 
[9] 
Rapuano, M.; Rosen, O.M. Phosphorylation of the insulin receptor by a casein kinase I-like enzyme. J. Biol. Chem.,  1991, 266(20), 12902-12907.
[http://dx.doi.org/10.1016/S0021-9258(18)98780-6] [PMID: 1649167] 
[10] 
Flotow, H.; Roach, P.J. Phosphate groups as substrate determinants for casein kinase I action. J. Biol. Chem.,  1989, 264, 9126-9128.
[http://dx.doi.org/10.1016/S0021-9258(18)60501-0] [PMID: 2498326] 
[11] 
Agostinis, P.; Marin, O.; James, P.; Hendrix, P.; Merlevede, W.; Vandenheede, J.R.; Pinna, L.A. Phosphorylation of the phosphatase modulator subunit (inhibitor-2) by casein kinase-1. Identification of the phosphorylation sites. FEBS Lett.,  1992, 305(2), 121-124.
[http://dx.doi.org/10.1016/0014-5793(92)80877-J] [PMID: 1319929] 
[12] 
Knippschild, U.; Milne, D.M.; Campbell, L.E.; DeMaggio, A.J.; Christenson, E.; Hoekstra, M.F.; Meek, D.W. p53 is phosphorylated in vitro and in vivo by the delta and epsilon isoforms of casein kinase 1 and enhances the level of casein kinase 1 delta in response to topoisomerase-directed drugs. Oncogene,  1997, 15(14), 1727-1736.
[http://dx.doi.org/10.1038/sj.onc.1201541] [PMID: 9349507] 
[13] 
Beyaert, R.; Vanhaesebroeck, B.; Declercq, W.; Van Lint, J.; Vandenabele, P.; Agostinis, P.; Vandenheede, J.R.; Fiers, W. Casein kinase-1 phosphorylates the p75 tumor necrosis factor receptor and negatively regulates tumor necrosis factor signaling for apoptosis. J. Biol. Chem.,  1995, 270(40), 23293-23299.
[http://dx.doi.org/10.1074/jbc.270.40.23293] [PMID: 7559483] 
[14] 
Barik, S.; Taylor, R.E.; Chakrabarti, D. Identification, cloning, and mutational analysis of the casein kinase 1 cDNA of the malaria parasite, Plasmodium falciparum. Stage-specific expression of the gene. J. Biol. Chem.,  1997, 272(42), 26132-26138.
[http://dx.doi.org/10.1074/jbc.272.42.26132] [PMID: 9334178] 
[15] 
Xu, R-M.; Carmel, G.; Sweet, R.M.; Kuret, J.; Cheng, X. Crystal structure of casein kinase-1, a phosphate-directed protein kinase. EMBO J.,  1995, 14(5), 1015-1023.
[http://dx.doi.org/10.1002/j.1460-2075.1995.tb07082.x] [PMID: 7889932] 
[16] 
Hirner, H.; Günes, C.; Bischof, J.; Wolff, S.; Grothey, A.; Kühl, M.; Oswald, F.; Wegwitz, F.; Bösl, M.R.; Trauzold, A.; Henne-Bruns, D.; Peifer, C.; Leithäuser, F.; Deppert, W.; Knippschild, U. Impaired CK1 delta activity attenuates SV40-induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo. PLoS One,  2012, 7(1), e29709.
[http://dx.doi.org/10.1371/journal.pone.0029709] [PMID: 22235331] 
[17] 
Mehlgarten, C.; Schaffrath, R. Mutant casein kinase I (Hrr25p/Kti14p) abrogates the G1 cell cycle arrest induced by Kluyveromyces lactiszymocin in budding yeast. Mol. Genet. Genomics,  2003, 269(2), 188-196.
[http://dx.doi.org/10.1007/s00438-003-0807-5] [PMID: 12756531] 
[18] 
Zeringo, N.A.; Murphy, L.; McCloskey, E.A.; Rohal, L.; Bellizzi, J.J. III A monoclinic crystal form of casein kinase 1δ. Acta Crystallographica Sect. F. Struct. Biol. Comm,  2013, 69, 1077-1083.
[19] 
Rivers, A.; Gietzen, K.F.; Vielhaber, E.; Virshup, D.M. Regulation of casein kinase Iε and casein kinase Iδ by an in vivo futile phosphorylation cycle. J. Biol. Chem.,  1998, 273(26), 15980-15984.
[http://dx.doi.org/10.1074/jbc.273.26.15980] [PMID: 9632646] 
[20] 
Endicott, J.A.; Noble, M.E.; Johnson, L.N. The structural basis for control of eukaryotic protein kinases. Annu. Rev. Biochem.,  2012, 81(1), 587-613.
[http://dx.doi.org/10.1146/annurev-biochem-052410-090317] [PMID: 22482904] 
[21] 
Peifer, C.; Abadleh, M.; Bischof, J.; Hauser, D.; Schattel, V.; Hirner, H.; Knippschild, U.; Laufer, S. 3,4-Diarylisoxazoles and -imidazoles as potent dual inhibitors of p38alpha mitogen activated protein kinase and casein kinase 1delta. J. Med. Chem.,  2009, 52(23), 7618-7630.
[http://dx.doi.org/10.1021/jm9005127] [PMID: 19591487] 
[22] 
Bischof, J.; Leban, J.; Zaja, M.; Grothey, A.; Radunsky, B.; Othersen, O.; Strobl, S.; Vitt, D.; Knippschild, U. 2-Benzamido-N-(1H-benzo[d]imidazol-2-yl)thiazole-4-carboxamide derivatives as potent inhibitors of CK1δ/ε. Amino Acids,  2012, 43(4), 1577-1591.
[http://dx.doi.org/10.1007/s00726-012-1234-x] [PMID: 22331384] 
[23] 
García-Reyes, B.; Witt, L.; Jansen, B.; Karasu, E.; Gehring, T.; Leban, J.; Henne-Bruns, D.; Pichlo, C.; Brunstein, E.; Baumann, U.; Wesseler, F.; Rathmer, B.; Schade, D.; Peifer, C.; Knippschild, U. Discovery of inhibitor of Wnt production 2 (IWP-2) and related compounds as selective ATP-competitive inhibitors of casein kinase 1 (CK1) delta/epsilon. J. Med. Chem.,  2018, 61(9), 4087-4102.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00095] [PMID: 29630366] 
[24] 
Löhler, J.; Hirner, H.; Schmidt, B.; Kramer, K.; Fischer, D.; Thal, D.R.; Leithäuser, F.; Knippschild, U. Immunohistochemical characterisation of cell-type specific expression of CK1delta in various tissues of young adult BALB/c mice. PLoS One,  2009, 4(1), e4174.
[http://dx.doi.org/10.1371/journal.pone.0004174] [PMID: 19137063] 
[25] 
Behrend, L.; Stöter, M.; Kurth, M.; Rutter, G.; Heukeshoven, J.; Deppert, W.; Knippschild, U. Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus. Eur. J. Cell Biol.,  2000, 79(4), 240-251.
[http://dx.doi.org/10.1078/S0171-9335(04)70027-8] [PMID: 10826492] 
[26] 
von Blume, J.; Knippschild, U.; Dequiedt, F.; Giamas, G.; Beck, A.; Auer, A.; Van Lint, J.; Adler, G.; Seufferlein, T. Phosphorylation at Ser244 by CK1 determines nuclear localization and substrate targeting of PKD2. EMBO J.,  2007, 26(22), 4619-4633.
[http://dx.doi.org/10.1038/sj.emboj.7601891] [PMID: 17962809] 
[27] 
Sillibourne, J.E.; Milne, D.M.; Takahashi, M.; Ono, Y.; Meek, D.W. Centrosomal anchoring of the protein kinase CK1delta mediated by attachment to the large, coiled-coil scaffolding protein CG-NAP/AKAP450. J. Mol. Biol.,  2002, 322(4), 785-797.
[http://dx.doi.org/10.1016/S0022-2836(02)00857-4] [PMID: 12270714] 
[28] 
Greer, Y.E.; Rubin, J.S. Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth. J. Cell Biol.,  2011, 192(6), 993-1004.
[http://dx.doi.org/10.1083/jcb.201011111] [PMID: 21422228] 
[29] 
Ianes, C.; Xu, P.; Werz, N.; Meng, Z.; Henne-Bruns, D.; Bischof, J.; Knippschild, U. CK1δ activity is modulated by CDK2/E- and CDK5/p35-mediated phosphorylation. Amino Acids,  2016, 48(2), 579-592.
[http://dx.doi.org/10.1007/s00726-015-2114-y] [PMID: 26464264] 
[30] 
Bischof, J.; Randoll, S.J.; Süßner, N.; Henne-Bruns, D.; Pinna, L.A.; Knippschild, U. CK1δ kinase activity is modulated by Chk1-mediated phosphorylation. PLoS One,  2013, 8(7), e68803.
[http://dx.doi.org/10.1371/journal.pone.0068803] [PMID: 23861943] 
[31] 
Longenecker, K.L.; Roach, P.J.; Hurley, T.D. Crystallographic studies of casein kinase I δ toward a structural understanding of auto-inhibition. Acta Crystallogr. D Biol. Crystallogr.,  1998, 54(Pt 3), 473-475.
[http://dx.doi.org/10.1107/S0907444997011724] [PMID: 9761932] 
[32] 
Giamas, G.; Hirner, H.; Shoshiashvili, L.; Grothey, A.; Gessert, S.; Kühl, M.; Henne-Bruns, D.; Vorgias, C.E.; Knippschild, U. Phosphorylation of CK1δ: identification of Ser370 as the major phosphorylation site targeted by PKA In vitro and in vivo. Biochem. J.,  2007, 406(3), 389-398.
[http://dx.doi.org/10.1042/BJ20070091] [PMID: 17594292] 
[33] 
Cunningham, P.S.; Ahern, S.A.; Smith, L.C.; da Silva Santos, C.S.; Wager, T.T.; Bechtold, D.A. Targeting of the circadian clock via CK1δ/ε to improve glucose homeostasis in obesity. Sci. Rep.,  2016, 6(1), 29983.
[http://dx.doi.org/10.1038/srep29983] [PMID: 27439882] 
[34] 
Sundaram, S.; Nagaraj, S.; Mahoney, H.; Portugues, A.; Li, W.; Millsaps, K.; Faulkner, J.; Yunus, A.; Burns, C.; Bloom, C.; Said, M.; Pinto, L.; Azam, S.; Flores, M.; Henriksen, A.; Gamsby, J.; Gulick, D. Inhibition of casein kinase 1δ/εimproves cognitive-affective behavior and reduces amyloid load in the APP-PS1 mouse model of Alzheimer’s disease. Sci. Rep.,  2019, 9(1), 13743.
[http://dx.doi.org/10.1038/s41598-019-50197-x] [PMID: 31551449] 
[35] 
De Lazzari, F.; Bisaglia, M.; Zordan, M.A.; Sandrelli, F. Circadian rhythm abnormalities in Parkinson’s disease from humans to flies and back. Int. J. Mol. Sci.,  2018, 19(12), 3911.
[http://dx.doi.org/10.3390/ijms19123911] [PMID: 30563246] 
[36] 
Lee, C.; Etchegaray, J.P.; Cagampang, F.R.A.; Loudon, A.S.I.; Reppert, S.M. Posttranslational mechanisms regulate the mammalian circadian clock. Cell,  2001, 107(7), 855-867.
[http://dx.doi.org/10.1016/S0092-8674(01)00610-9] [PMID: 11779462] 
[37] 
Aryal, R.P.; Kwak, P.B.; Tamayo, A.G.; Gebert, M.; Chiu, P-L.; Walz, T.; Weitz, C.J. Macromolecular assemblies of the mammalian circadian clock. Mol. Cell,  2017, 67(5), 770-782.e6.
[http://dx.doi.org/10.1016/j.molcel.2017.07.017] [PMID: 28886335] 
[38] 
Etchegaray, J.P.; Machida, K.K.; Noton, E.; Constance, C.M.; Dallmann, R.; Di Napoli, M.N.; DeBruyne, J.P.; Lambert, C.M.; Yu, E.A.; Reppert, S.M.; Weaver, D.R. Casein kinase 1 delta regulates the pace of the mammalian circadian clock. Mol. Cell. Biol.,  2009, 29(14), 3853-3866.
[http://dx.doi.org/10.1128/MCB.00338-09] [PMID: 19414593] 
[39] 
Fustin, J-M.; Kojima, R.; Itoh, K.; Chang, H-Y.; Ye, S.; Zhuang, B.; Oji, A.; Gibo, S.; Narasimamurthy, R.; Virshup, D.; Kurosawa, G.; Doi, M.; Manabe, I.; Ishihama, Y.; Ikawa, M.; Okamura, H. Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock. Proc. Natl. Acad. Sci. USA,  2018, 115(23), 5980-5985.
[http://dx.doi.org/10.1073/pnas.1721371115] [PMID: 29784786] 
[40] 
Wood, P.A.; Yang, X.; Taber, A.; Oh, E.Y.; Ansell, C.; Ayers, S.E.; Al-Assaad, Z.; Carnevale, K.; Berger, F.G.; Peña, M.M.; Hrushesky, W.J. Period 2 mutation accelerates ApcMin/+ tumorigenesis. Mol. Cancer Res.,  2008, 6(11), 1786-1793.
[http://dx.doi.org/10.1158/1541-7786.MCR-08-0196] [PMID: 19010825] 
[41] 
Shafi, A.A.; McNair, C.M.; McCann, J.J.; Alshalalfa, M.; Shostak, A.; Severson, T.M.; Zhu, Y.; Bergman, A.; Gordon, N.; Mandigo, A.C.; Chand, S.N.; Gallagher, P.; Dylgjeri, E.; Laufer, T.S.; Vasilevskaya, I.A.; Schiewer, M.J.; Brunner, M.; Feng, F.Y.; Zwart, W.; Knudsen, K.E. The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair. Nat. Commun.,  2021, 12(1), 401.
[http://dx.doi.org/10.1038/s41467-020-20513-5] [PMID: 33452241] 
[42] 
Winter, M.; Milne, D.; Dias, S.; Kulikov, R.; Knippschild, U.; Blattner, C.; Meek, D. Protein kinase CK1δ phosphorylates key sites in the acidic domain of murine double-minute clone 2 protein (MDM2) that regulate p53 turnover. Biochemistry,  2004, 43(51), 16356-16364.
[http://dx.doi.org/10.1021/bi0489255] [PMID: 15610030] 
[43] 
Inuzuka, H.; Fukushima, H.; Shaik, S.; Wei, W. Novel insights into the molecular mechanisms governing Mdm2 ubiquitination and destruction. Oncotarget,  2010, 1(7), 685-690.
[http://dx.doi.org/10.18632/oncotarget.202] [PMID: 21317463] 
[44] 
Kalousi, A.; Mylonis, I.; Politou, A.S.; Chachami, G.; Paraskeva, E.; Simos, G. Casein kinase 1 regulates human hypoxia-inducible factor HIF-1. J. Cell Sci.,  2010, 123(Pt 17), 2976-2986.
[http://dx.doi.org/10.1242/jcs.068122] [PMID: 20699359] 
[45] 
Behrend, L.; Milne, D.M.; Stöter, M.; Deppert, W.; Campbell, L.E.; Meek, D.W.; Knippschild, U. 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, 19(47), 5303-5313.
[http://dx.doi.org/10.1038/sj.onc.1203939] [PMID: 11103931] 
[46] 
Greer, Y.E.; Gao, B.; Yang, Y.; Nussenzweig, A.; Rubin, J.S. Lack of casein kinase 1 Delta promotes genomic instability, the accumulation of DNA damage and down-regulation of checkpoint kinase 1. PLoS One,  2017, 12(1), e0170903.
[http://dx.doi.org/10.1371/journal.pone.0170903] [PMID: 28125685] 
[47] 
Penas, C.; Ramachandran, V.; Simanski, S.; Lee, C.; Madoux, F.; Rahaim, R.J.; Chauhan, R.; Barnaby, O.; Schurer, S.; Hodder, P.; Steen, J.; Roush, W.R.; Ayad, N.G. Casein kinase 1δ-dependent Wee1 protein degradation. J. Biol. Chem.,  2014, 289(27), 18893-18903.
[http://dx.doi.org/10.1074/jbc.M114.547661] [PMID: 24817118] 
[48] 
Greer, Y.E.; Westlake, C.J.; Gao, B.; Bharti, K.; Shiba, Y.; Xavier, C.P.; Pazour, G.J.; Yang, Y.; Rubin, J.S. Casein kinase 1δ functions at the centrosome and Golgi to promote ciliogenesis. Mol. Biol. Cell,  2014, 25(10), 1629-1640.
[http://dx.doi.org/10.1091/mbc.e13-10-0598] [PMID: 24648492] 
[49] 
Knippschild, U.; Wolff, S.; Giamas, G.; Brockschmidt, C.; Wittau, M.; Würl, P.U.; Eismann, T.; Stöter, M.; Würl, P.U.; Stöter, M. The role of the casein kinase 1 (CK1) family in different signaling pathways linked to cancer development. Onkologie,  2005, 28(10), 508-514.
[PMID: 16186692] 
[50] 
Cruciat, C-M. Casein kinase 1 and Wnt/β-catenin signaling. Curr. Opin. Cell Biol.,  2014, 31, 46-55.
[http://dx.doi.org/10.1016/j.ceb.2014.08.003] [PMID: 25200911] 
[51] 
Ciani, L.; Salinas, P.C. WNTs in the vertebrate nervous system: From patterning to neuronal connectivity. Nat. Rev. Neurosci.,  2005, 6(5), 351-362.
[http://dx.doi.org/10.1038/nrn1665] [PMID: 15832199] 
[52] 
Nusse, R.; Clevers, H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell,  2017, 169(6), 985-999.
[http://dx.doi.org/10.1016/j.cell.2017.05.016] [PMID: 28575679] 
[53] 
Libro, R.; Bramanti, P.; Mazzon, E. The role of the Wnt canonical signaling in neurodegenerative diseases. Life Sci.,  2016, 158, 78-88.
[http://dx.doi.org/10.1016/j.lfs.2016.06.024] [PMID: 27370940] 
[54] 
Shi, J.; Chi, S.; Xue, J.; Yang, J.; Li, F.; Liu, X. Emerging role and therapeutic implication of Wnt signaling pathways in autoimmune diseases. J. Immunol. Res.,  2016, 2016, 9392132.
[http://dx.doi.org/10.1155/2016/9392132] [PMID: 27110577] 
[55] 
Schittek, B.; Sinnberg, T. Biological functions of casein kinase 1 isoforms and putative roles in tumorigenesis. Mol. Cancer,  2014, 13(1), 231.
[http://dx.doi.org/10.1186/1476-4598-13-231] [PMID: 25306547] 
[56] 
Jiang, J.; Hui, C.C. Hedgehog signaling in development and cancer. Dev. Cell,  2008, 15(6), 801-812.
[http://dx.doi.org/10.1016/j.devcel.2008.11.010] [PMID: 19081070] 
[57] 
Knippschild, U.; Krüger, M.; Richter, J.; Xu, P.; García-Reyes, B.; Peifer, C.; Halekotte, J.; Bakulev, V.; Bischof, J. The CK1 family: contribution to cellular stress response and its role in carcinogenesis. Front. Oncol.,  2014, 4, 96.
[http://dx.doi.org/10.3389/fonc.2014.00096] [PMID: 24904820] 
[58] 
Tsai, I.C.; Woolf, M.; Neklason, D.W.; Branford, W.W.; Yost, H.J.; Burt, R.W.; Virshup, D.M. Disease-associated casein kinase I δ mutation may promote adenomatous polyps formation via a Wnt/β-catenin independent mechanism. Int. J. Cancer,  2007, 120(5), 1005-1012.
[http://dx.doi.org/10.1002/ijc.22368] [PMID: 17131344] 
[59] 
Richter, J.; Rudeck, S.; Kretz, A.L.; Kramer, K.; Just, S.; Henne-Bruns, D.; Hillenbrand, A.; Leithäuser, F.; Lemke, J.; Knippschild, U. Decreased CK1δ expression predicts prolonged survival in colorectal cancer patients. Tumour Biol.,  2016, 37(7), 8731-8739.
[http://dx.doi.org/10.1007/s13277-015-4745-8] [PMID: 26738869] 
[60] 
Cheong, J.K.; Nguyen, T.H.; Wang, H.; Tan, P.; Voorhoeve, P.M.; Lee, S.H.; Virshup, D.M. IC261 induces cell cycle arrest and apoptosis of human cancer cells via CK1δ/ɛ and Wnt/β-catenin independent inhibition of mitotic spindle formation. Oncogene,  2011, 30(22), 2558-2569.
[http://dx.doi.org/10.1038/onc.2010.627] [PMID: 21258417] 
[61] 
Xu, Y.; Toh, K.L.; Jones, C.R.; Shin, J.Y.; Fu, Y.H.; Ptácek, L.J. Modeling of a human circadian mutation yields insights into clock regulation by PER2. Cell,  2007, 128(1), 59-70.
[http://dx.doi.org/10.1016/j.cell.2006.11.043] [PMID: 17218255] 
[62] 
Adler, P.; Mayne, J.; Walker, K.; Ning, Z.; Figeys, D. Therapeutic targeting of casein kinase 1δ/ε in an Alzheimer’s disease mouse model. J. Proteome Res.,  2019, 18(9), 3383-3393.
[http://dx.doi.org/10.1021/acs.jproteome.9b00312] [PMID: 31334659] 
[63] 
Yasojima, K.; Kuret, J.; DeMaggio, A.J.; McGeer, E.; McGeer, P.L. Casein kinase 1 delta mRNA is upregulated in Alzheimer’s disease brain. Brain Res.,  2000, 865(1), 116-120.
[http://dx.doi.org/10.1016/S0006-8993(00)02200-9] [PMID: 10814741] 
[64] 
Li, G.; Yin, H.; Kuret, J. Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules. J. Biol. Chem.,  2004, 279(16), 15938-15945.
[http://dx.doi.org/10.1074/jbc.M314116200] [PMID: 14761950] 
[65] 
Chen, C.; Gu, J.; Basurto-Islas, G.; Jin, N.; Wu, F.; Cheng-Xin, G.; Iqbal, K.; Liu, F. Up-regulation of CK1ε is involved in tau pathogenesis in Alzheimer’s disease. Sci. Rep.,  2017, 7, 13478.
[http://dx.doi.org/10.1038/s41598-017-13791-5] [PMID: 29044200] 
[66] 
Flajolet, M.; He, G.; Heiman, M.; Lin, A.; Nairn, A.C.A.; Greengard, P. Regulation of Alzheimer’s disease amyloid-β formation by casein kinase I. Proc. Natl. Acad. Sci. USA,  2007, 104(10), 4159-4164.
[http://dx.doi.org/10.1073/pnas.0611236104] [PMID: 17360493] 
[67] 
Chang, X.L.; Tan, M.S.; Tan, L.; Yu, J.T. The role of TDP-43 in Alzheimer’s disease. Mol. Neurobiol.,  2016, 53(5), 3349-3359.
[http://dx.doi.org/10.1007/s12035-015-9264-5] [PMID: 26081142] 
[68] 
Thal, D.R.; Del Tredici, K.; Ludolph, A.C.; Hoozemans, J.J.; Rozemuller, A.J.; Braak, H.; Knippschild, U. Stages of granulovacuolar degeneration: Their relation to Alzheimer’s disease and chronic stress response. Acta Neuropathol.,  2011, 122(5), 577-589.
[http://dx.doi.org/10.1007/s00401-011-0871-6] [PMID: 21935637] 
[69] 
Nonaka, T.; Suzuki, G.; Tanaka, Y.; Kametani, F.; Hirai, S.; Okado, H.; Miyashita, T.; Saitoe, M.; Akiyama, H.; Masai, H.; Hasegawa, M. Phosphorylation of TAR DNA-binding protein of 43 kD (TDP-43) by truncated casein kinase 1δ triggers mislocalization and accumulation of TDP-43. J. Biol. Chem.,  2016, 291(11), 5473-5483.
[http://dx.doi.org/10.1074/jbc.M115.695379] [PMID: 26769969] 
[70] 
Martínez-González, L.; Rodríguez-Cueto, C.; Cabezudo, D.; Bartolomé, F.; Andrés-Benito, P.; Ferrer, I.; Gil, C.; Martín-Requero, Á.; Fernández-Ruiz, J.; Martínez, A. de Lago, E Motor neuron preservation and decrease of in vivo TDP-43 phosphorylation by protein CK-1 kinase inhibitor treatment. Sci. Rep.,  2020, 10, 4449.
[http://dx.doi.org/10.1038/s41598-020-61265-y] [PMID: 32157143] 
[71] 
Mackenzie, I.R.; Rademakers, R.; Neumann, M. TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. Lancet Neurol.,  2010, 9(10), 995-1007.
[http://dx.doi.org/10.1016/S1474-4422(10)70195-2] [PMID: 20864052] 
[72] 
Alquezar, C.; Salado, I.G.; de la Encarnación, A.; Pérez, D.I.; Moreno, F.; Gil, C.; de Munain, A.L.; Martínez, A.; Martín-Requero, Á. Targeting TDP-43 phosphorylation by Casein Kinase-1δ inhibitors: A novel strategy for the treatment of frontotemporal dementia. Mol. Neurodegener.,  2016, 11(1), 36.
[http://dx.doi.org/10.1186/s13024-016-0102-7] [PMID: 27138926] 
[73] 
Arai, T.; Mackenzie, I.R.; Hasegawa, M.; Nonoka, T.; Niizato, K.; Tsuchiya, K.; Iritani, S.; Onaya, M.; Akiyama, H. Phosphorylated TDP-43 in Alzheimer’s disease and dementia with Lewy bodies. Acta Neuropathol.,  2009, 117(2), 125-136.
[http://dx.doi.org/10.1007/s00401-008-0480-1] [PMID: 19139911] 
[74] 
He, S.; Wang, F.; Yung, K.K.L.; Zhang, S.; Qu, S. Effects of α-Synuclein-associated post-translational modifications in Parkinson’s disease. ACS Chem. Neurosci.,  2021, 12(7), 1061-1071.
[http://dx.doi.org/10.1021/acschemneuro.1c00028] [PMID: 33769791] 
[75] 
Okochi, M.; Walter, J.; Koyama, A.; Nakajo, S.; Baba, M.; Iwatsubo, T.; Meijer, L.; Kahle, P.J.; Haass, C. Constitutive phosphorylation of the Parkinson’s disease associated alpha-synuclein. J. Biol. Chem.,  2000, 275(1), 390-397.
[http://dx.doi.org/10.1074/jbc.275.1.390] [PMID: 10617630] 
[76] 
Lippa, C.F.; Fujiwara, H.; Mann, D.M.; Giasson, B.; Baba, M.; Schmidt, M.L.; Nee, L.E.; O’Connell, B.; Pollen, D.A.; St George-Hyslop, P.; Ghetti, B.; Nochlin, D.; Bird, T.D.; Cairns, N.J.; Lee, V.M.; Iwatsubo, T.; Trojanowski, J.Q. Lewy bodies contain altered α-synuclein in brains of many familial Alzheimer’s disease patients with mutations in presenilin and amyloid precursor protein genes. Am. J. Pathol.,  1998, 153(5), 1365-1370.
[http://dx.doi.org/10.1016/S0002-9440(10)65722-7] [PMID: 9811326] 
[77] 
Paleologou, K.E.; Oueslati, A.; Shakked, G.; Rospigliosi, C.C.; Kim, H.Y.; Lamberto, G.R.; Fernandez, C.O.; Schmid, A.; Chegini, F.; Gai, W.P.; Chiappe, D.; Moniatte, M.; Schneider, B.L.; Aebischer, P.; Eliezer, D.; Zweckstetter, M.; Masliah, E.; Lashuel, H.A. Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions. J. Neurosci.,  2010, 30(9), 3184-3198.
[http://dx.doi.org/10.1523/JNEUROSCI.5922-09.2010] [PMID: 20203178] 
[78] 
Chakraborty, J.; Basso, V.; Ziviani, E. Post translational modification of Parkin. Biol. Direct,  2017, 12(1), 6.
[http://dx.doi.org/10.1186/s13062-017-0176-3] [PMID: 28222786] 
[79] 
Rubio de la Torre, E.; Luzón-Toro, B.; Forte-Lago, I.; Minguez-Castellanos, A.; Ferrer, I.; Hilfiker, S. Combined kinase inhibition modulates parkin inactivation. Hum. Mol. Genet.,  2009, 18(5), 809-823.
[PMID: 19050041] 
[80] 
Traxler, P.; Furet, P. Strategies toward the design of novel and selective protein tyrosine kinase inhibitors. Pharmacol. Ther.,  1999, 82(2-3), 195-206.
[http://dx.doi.org/10.1016/S0163-7258(98)00044-8] [PMID: 10454197] 
[81] 
Mashhoon, N.; DeMaggio, A.J.; Tereshko, V.; Bergmeier, S.C.; Egli, M.; Hoekstra, M.F.; Kuret, J. Crystal structure of a conformation-selective casein kinase-1 inhibitor. J. Biol. Chem.,  2000, 275(26), 20052-20060.
[http://dx.doi.org/10.1074/jbc.M001713200] [PMID: 10749871] 
[82] 
Brockschmidt, C.; Hirner, H.; Huber, N.; Eismann, T.; Hillenbrand, A.; Giamas, G.; Radunsky, B.; Ammerpohl, O.; Bohm, B.; Henne-Bruns, D.; Kalthoff, H.; Leithäuser, F.; Trauzold, A.; Knippschild, U. Anti-apoptotic and growth-stimulatory functions of CK1 delta and epsilon in ductal adenocarcinoma of the pancreas are inhibited by IC261 in vitro and in vivo. Gut,  2008, 57(6), 799-806.
[http://dx.doi.org/10.1136/gut.2007.123695] [PMID: 18203806] 
[83] 
Stöter, M.; Krüger, M.; Banting, G.; Henne-Bruns, D.; Knippschild, U. Microtubules depolymerization caused by the CK1 inhibitor IC261 may be not mediated by CK1 blockage. PLoS One,  2014, 9(6), e100090.
[http://dx.doi.org/10.1371/journal.pone.0100090] [PMID: 24937750] 
[84] 
Liu, M.; Hu, Y.; Lu, S.; Lu, M.; Li, J.; Chang, H.; Jia, H.; Zhou, M.; Ren, F.; Zhong, J. IC261, a specific inhibitor of CK1δ/ε, promotes aerobic glycolysis through p53-dependent mechanisms in colon cancer. Int. J. Biol. Sci.,  2020, 16(5), 882-892.
[http://dx.doi.org/10.7150/ijbs.40960] [PMID: 32071557] 
[85] 
Cozza, G.; Gianoncelli, A.; Montopoli, M.; Caparrotta, L.; Venerando, A.; Meggio, F.; Pinna, L.A.; Zagotto, G.; Moro, S. Identification of novel protein kinase CK1 delta (CK1delta) inhibitors through structure-based virtual screening. Bioorg. Med. Chem. Lett.,  2008, 18(20), 5672-5675.
[http://dx.doi.org/10.1016/j.bmcl.2008.08.072] [PMID: 18799313] 
[86] 
Rena, G.; Bain, J.; Elliott, M.; Cohen, P. D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a. EMBO Rep.,  2004, 5(1), 60-65.
[http://dx.doi.org/10.1038/sj.embor.7400048] [PMID: 14710188] 
[87] 
Badura, L.; Swanson, T.; Adamowicz, W.; Adams, J.; Cianfrogna, J.; Fisher, K.; Holland, J.; Kleiman, R.; Nelson, F.; Reynolds, L.; St Germain, K.; Schaeffer, E.; Tate, B.; Sprouse, J. An inhibitor of casein kinase Iε induces phase delays in circadian rhythms under free-running and entrained conditions. J. Pharmacol. Exp. Ther.,  2007, 322(2), 730-738.
[http://dx.doi.org/10.1124/jpet.107.122846] [PMID: 17502429] 
[88] 
Long, A.; Zhao, H.; Huang, X. Structural basis for the interaction between casein kinase 1 delta and a potent and selective inhibitor. J. Med. Chem.,  2012, 55(2), 956-960.
[http://dx.doi.org/10.1021/jm201387s] [PMID: 22168824] 
[89] 
Janovska, P.; Verner, J.; Kohoutek, J.; Bryjova, L.; Gregorova, M.; Dzimkova, M.; Skabrahova, H.; Radaszkiewicz, T.; Ovesna, P.; Vondalova Blanarova, O.; Nemcova, T.; Hoferova, Z.; Vasickova, K.; Smyckova, L.; Egle, A.; Pavlova, S.; Poppova, L.; Plevova, K.; Pospisilova, S.; Bryja, V. Casein kinase 1 is a therapeutic target in chronic lymphocytic leukemia. Blood,  2018, 131(11), 1206-1218.
[http://dx.doi.org/10.1182/blood-2017-05-786947] [PMID: 29317454] 
[90] 
Fernandez, I.E.; Eickelberg, O. New cellular and molecular mechanisms of lung injury and fibrosis in idiopathic pulmonary fibrosis. Lancet,  2012, 380(9842), 680-688.
[http://dx.doi.org/10.1016/S0140-6736(12)61144-1] [PMID: 22901889] 
[91] 
Keenan, C.R.; Langenbach, S.Y.; Jativa, F.; Harris, T.; Li, M.; Chen, Q.; Xia, Y.; Gao, B.; Schuliga, M.J.; Jaffar, J.; Prodanovic, D.; Tu, Y.; Berhan, A.; Lee, P.V.S.; Westall, G.P.; Stewart, A.G. Casein Kinase 1δ/ε inhibitor, PF670462 attenuates the fibrogenic effects of transforming growth factor-β in pulmonary fibrosis. Front. Pharmacol.,  2018, 9, 738.
[http://dx.doi.org/10.3389/fphar.2018.00738] [PMID: 30042678] 
[92] 
Wager, T.T.; Chandrasekaran, R.Y.; Bradley, J.; Rubitski, D.; Berke, H.; Mente, S.; Butler, T.; Doran, A.; Chang, C.; Fisher, K.; Knafels, J.; Liu, S.; Ohren, J.; Marconi, M.; DeMarco, G.; Sneed, B.; Walton, K.; Horton, D.; Rosado, A.; Mead, A. Casein kinase 1δ/ε inhibitor PF-5006739 attenuates opioid drug-seeking behavior. ACS Chem. Neurosci.,  2014, 5(12), 1253-1265.
[http://dx.doi.org/10.1021/cn500201x] [PMID: 25299732] 
[93] 
Peifer, C.; Kinkel, K.; Abadleh, M.; Schollmeyer, D.; Laufer, S. From five- to six-membered rings: 3,4-diarylquinolinone as lead for novel p38MAP kinase inhibitors. J. Med. Chem.,  2007, 50(6), 1213-1221.
[http://dx.doi.org/10.1021/jm061097o] [PMID: 17323937] 
[94] 
Peifer, C.; Urich, R.; Schattel, V.; Abadleh, M.; Röttig, M.; Kohlbacher, O.; Laufer, S. Implications for selectivity of 3,4-diarylquinolinones as p38alphaMAP kinase inhibitors. Bioorg. Med. Chem. Lett.,  2008, 18(4), 1431-1435.
[http://dx.doi.org/10.1016/j.bmcl.2007.12.073] [PMID: 18207396] 
[95] 
Luxenburger, A.; Schmidt, D.; Ianes, C.; Pichlo, C.; Krüger, M.; von Drathen, T.; Brunstein, E.; Gainsford, G.J.; Baumann, U.; Knippschild, U.; Peifer, C. Design, synthesis and biological evaluation of isoxazole-based CK1 inhibitors modified with chiral pyrrolidine scaffolds. Molecules,  2019, 24(5), 873.
[http://dx.doi.org/10.3390/molecules24050873] [PMID: 30832206] 
[96] 
Peifer, C.; Wagner, G.; Laufer, S. New approaches to the treatment of inflammatory disorders small molecule inhibitors of p38 MAP kinase. Curr. Top. Med. Chem.,  2006, 6(2), 113-149.
[http://dx.doi.org/10.2174/156802606775270323] [PMID: 16454763] 
[97] 
Halekotte, J.; Witt, L.; Ianes, C.; Krüger, M.; Bührmann, M.; Rauh, D.; Pichlo, C.; Brunstein, E.; Luxenburger, A.; Baumann, U.; Knippschild, U.; Bischof, J.; Peifer, C. Optimized 4,5-diarylimidazoles as potent/selective inhibitors of protein kinase CK1δ and their structural relation to p38α MAPK. Molecules,  2017, 22(4), 522.
[http://dx.doi.org/10.3390/molecules22040522] [PMID: 28338621] 
[98] 
Seerden, J-P.G.; Leusink-Ionescu, G.; Woudenberg-Vrenken, T.; Bas, D.; Molema, G.; Kamps, J.A.A.M.; Kellogg, R.M. Synthesis and structure-activity relationships of 4-fluorophenyl-imidazole p38a MAPK, CK1δ and JAK2 kinase inhibitors. Bioorg. Med. Chem. Lett.,  2014, 24, 3412-3418.
[http://dx.doi.org/10.1016/j.bmcl.2014.05.080] [PMID: 24930833] 
[99] 
Mente, S.; Arnold, E.; Butler, T.; Chakrapani, S.; Chandrasekaran, R.; Cherry, K.; DiRico, K.; Doran, A.; Fisher, K.; Galatsis, P.; Green, M.; Hayward, M.; Humphrey, J.; Knafels, J.; Li, J.; Liu, S.; Marconi, M.; McDonald, S.; Ohren, J.; Paradis, V.; Sneed, B.; Walton, K.; Wager, T. Ligand-protein interactions of selective casein kinase 1δ inhibitors. J. Med. Chem.,  2013, 56(17), 6819-6828.
[http://dx.doi.org/10.1021/jm4006324] [PMID: 23919824] 
[100] 
Wager, T.T.; Galatsis, P.; Chandrasekaran, R.Y.; Butler, T.W.; Li, J.; Zhang, L.; Mente, S.; Subramanyam, C.; Liu, S.; Doran, A.C.; Chang, C.; Fisher, K.; Grimwood, S.; Hedde, J.R.; Marconi, M.; Schildknegt, K. Identification and profiling of a selective and brain penetrant radioligand forvia target occupancy measurement of casein kinase 1 inhibitors. ACS Chem. Neurosci.,  2017, 8(9), 1995-2004.
[http://dx.doi.org/10.1021/acschemneuro.7b00155] [PMID: 28609096] 
[101] 
Oumata, N.; Bettayeb, K.; Ferandin, Y.; Demange, L.; Lopez-Giral, A.; Goddard, M.L.; Myrianthopoulos, V.; Mikros, E.; Flajolet, M.; Greengard, P.; Meijer, L.; Galons, H. Roscovitine-derived, dual-specificity inhibitors of cyclin-dependent kinases and casein kinases 1. J. Med. Chem.,  2008, 51(17), 5229-5242.
[http://dx.doi.org/10.1021/jm800109e] [PMID: 18698753] 
[102] 
Hirota, T.; Lee, J.W.; Lewis, W.G.; Zhang, E.E.; Breton, G.; Liu, X.; Garcia, M.; Peters, E.C.; Etchegaray, J-P.; Traver, D.; Schultz, P.G.; Kay, S.A. High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms. PLoS Biol.,  2010, 8, e1000559.
[http://dx.doi.org/10.1371/journal.pbio.1000559] [PMID: 21179498] 
[103] 
Yanpeng, X.; Liang, Z.; Zijie, S.; Jiaxing, S. Sun, Qi; Shan-Shan, L.; Yuqing, X.; Zhongyuan, W.; Desheng, L. Longdaysin inhibits Wnt/β-catenin signaling and exhibits antitumor activity against breast cancer. OncoTargets Ther.,  2019, 12, 993-1005.
[http://dx.doi.org/10.2147/OTT.S193024] 
[104] 
Bibian, M.; Rahaim, R.J.; Choi, J.Y.; Noguchi, Y.; Schürer, S.; Chen, W.; Nakanishi, S.; Licht, K.; Rosenberg, L.H.; Li, L.; Feng, Y.; Cameron, M.D.; Duckett, D.R.; Cleveland, J.L.; Roush, W.R. Development of highly selective casein kinase 1δ/1ε (CK1δ/ε) inhibitors with potent antiproliferative properties. Bioorg. Med. Chem. Lett.,  2013, 23(15), 4374-4380.
[http://dx.doi.org/10.1016/j.bmcl.2013.05.075] [PMID: 23787102] 
[105] 
Monastyrskyi, A.; Nilchan, N.; Quereda, V.; Noguchi, Y.; Ruiz, C.; Grant, W.; Cameron, M.; Duckett, D.; Roush, W. Development of dual casein kinase 1δ/1ε (CK1δ/ε) inhibitors for treatment of breast cancer. Bioorg. Med. Chem.,  2018, 26(3), 590-602.
[http://dx.doi.org/10.1016/j.bmc.2017.12.020] [PMID: 29289448] 
[106] 
Rosenberg, L.H.; Lafitte, M.; Quereda, V.; Grant, W.; Chen, W.; Bibian, M.; Noguchi, Y.; Fallahi, M.; Yang, C.; Chang, J.C.; Roush, W.R.; Cleveland, J.L.; Duckett, D.R. Therapeutic targeting of casein kinase 1δ in breast cancer. Sci. Transl. Med.,  2015, 7(318), 318ra202.
[http://dx.doi.org/10.1126/scitranslmed.aac8773] [PMID: 26676609] 
[107] 
Redenti, S.; Marcovich, I.; De Vita, T.; Pérez, C.; De Zorzi, R.; Demitri, N.; Perez, D.I.; Bottegoni, G.; Bisignano, P.; Bissaro, M.; Moro, S.; Martinez, A.; Storici, P.; Spalluto, G.; Cavalli, A.; Federico, S. A Triazolotriazine-based dual GSK-3b/CK-1δ ligand as a potential neuroprotective agent presenting two different mechanisms of enzymatic inhibition. ChemMedChem,  2019, 14(3), 310-314.
[http://dx.doi.org/10.1002/cmdc.201800778] [PMID: 30548443] 
[108] 
Grieco, I.; Bissaro, M.; Tiz, D.B.; Perez, D.I.; Perez, C.; Martinez, A.; Redenti, S.; Mariotto, E.; Bortolozzi, R.; Viola, G.; Cozza, G.; Spalluto, G.; Moro, S.; Federico, S. Developing novel classes of protein kinase CK1δ inhibitors by fusing [1,2,4]triazole with different bicyclic heteroaromatic systems. Eur. J. Med. Chem.,  2021, 216, 113331.
[http://dx.doi.org/10.1016/j.ejmech.2021.113331] [PMID: 33721670] 
[109] 
Liu, Y.M.; Chen, C.H.; Yeh, T.K.; Liou, J.P. Synthesis and evaluation of novel 7H-pyrrolo-[2,3-d]pyrimidine derivatives as potential anticancer agents. Future Med. Chem.,  2019, 11(9), 959-974.
[http://dx.doi.org/10.4155/fmc-2018-0564] [PMID: 30789758] 
[110] 
Chen, C.H.; Liu, Y.M.; Pan, S.L.; Liu, Y.R.; Liou, J.P.; Yen, Y. Trichlorobenzene-substituted azaaryl compounds as novel FGFR inhibitors exhibiting potent antitumor activity in bladder cancer cells in vitro and in vivo. Oncotarget,  2016, 7(18), 26374-26387.
[http://dx.doi.org/10.18632/oncotarget.8380] [PMID: 27029060] 
[111] 
Leban, J.; Baierl, M.; Mies, J.; Trentinaglia, V.; Rath, S.; Kronthaler, K.; Wolf, K.; Gotschlich, A.; Seifert, M.H. A novel class of potent NF-kappaB signaling inhibitors. Bioorg. Med. Chem. Lett.,  2007, 17(21), 5858-5862.
[http://dx.doi.org/10.1016/j.bmcl.2007.08.022] [PMID: 17869512] 
[112] 
Richter, J.; Bischof, J.; Zaja, M.; Kohlhof, H.; Othersen, O.; Vitt, D.; Alscher, V.; Pospiech, I.; García-Reyes, B.; Berg, S.; Leban, J.; Knippschild, U. Difluoro-dioxolo-benzoimidazol-benzamides as potent inhibitors of CK1δ and ε with nanomolar inhibitory activity on cancer cell proliferation. J. Med. Chem.,  2014, 57(19), 7933-7946.
[http://dx.doi.org/10.1021/jm500600b] [PMID: 25191940] 
[113] 
Walsh, D.P.; Chang, Y.T. Chemical genetics. Chem. Rev.,  2006, 106(6), 2476-2530.
[http://dx.doi.org/10.1021/cr0404141] [PMID: 16771457] 
[114] 
Salado, I.G.; Redondo, M.; Bello, M.L.; Perez, C.; Liachko, N.F.; Kraemer, B.C.; Miguel, L.; Lecourtois, M.; Gil, C.; Martinez, A.; Perez, D.I. Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis. J. Med. Chem.,  2014, 57(6), 2755-2772.
[http://dx.doi.org/10.1021/jm500065f] [PMID: 24592867] 
[115] 
Neumann, M.; Sampathu, D.M.; Kwong, L.K.; Truax, A.C.; Micsenyi, M.C.; Chou, T.T.; Bruce, J.; Schuck, T.; Grossman, M.; Clark, C.M.; McCluskey, L.F.; Miller, B.L.; Masliah, E.; Mackenzie, I.R.; Feldman, H.; Feiden, W.; Kretzschmar, H.A.; Trojanowski, J.Q.; Lee, V.M. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science,  2006, 314(5796), 130-133.
[http://dx.doi.org/10.1126/science.1134108] [PMID: 17023659] 
[116] 
Wang, X.; Moon, J.; Dodge, M.E.; Pan, X.; Zhang, L.; Hanson, J.M.; Tuladhar, R.; Ma, Z.; Shi, H.; Williams, N.S.; Amatruda, J.F.; Carroll, T.J.; Lum, L.; Chen, C. The development of highly potent inhibitors for porcupine. J. Med. Chem.,  2013, 56(6), 2700-2704.
[http://dx.doi.org/10.1021/jm400159c] [PMID: 23477365] 
[117] 
Kumar, A.; Rajendran, V.; Sethumadhavan, R.; Purohit, R. Relationship between a point mutation S97C in CK1δ protein and its affect on ATP-binding affinity. J. Biomol. Struct. Dyn.,  2014, 32(3), 394-405.
[http://dx.doi.org/10.1080/07391102.2013.770373] [PMID: 23527964] 
[118] 
Richter, J.; Ullah, K.; Xu, P.; Alscher, V.; Blatz, A.; Peifer, C.; Halekotte, J.; Leban, J.; Vitt, D.; Holzmann, K.; Bakulev, V.; Pinna, L.A.; Henne-Bruns, D.; Hillenbrand, A.; Kornmann, M.; Leithäuser, F.; Bischof, J.; Knippschild, U. Effects of altered expression and activity levels of CK1δ and ɛ on tumor growth and survival of colorectal cancer patients. Int. J. Cancer,  2015, 136(12), 2799-2810.
[http://dx.doi.org/10.1002/ijc.29346] [PMID: 25404202] 
[119] 
Liu, C.; Witt, L.; Ianes, C.; Bischof, J.; Bammert, M.T.; Baier, J.; Kirschner, S.; Henne-Bruns, D.; Xu, P.; Kornmann, M.; Peifer, C.; Knippschild, U. Newly developed CK1-specific inhibitors show specifically stronger effects on CK1 mutants and colon cancer cell lines. Int. J. Mol. Sci.,  2019, 20(24), 6184.
[http://dx.doi.org/10.3390/ijms20246184] [PMID: 31817920] 
[120] 
Sreedharan, J.; Blair, I.P.; Tripathi, V.B.; Hu, X.; Vance, C.; Rogelj, B.; Ackerley, S.; Durnall, J.C.; Williams, K.L.; Buratti, E.; Baralle, F.; de Belleroche, J.; Mitchell, J.D.; Leigh, P.N.; Al-Chalabi, A.; Miller, C.C.; Nicholson, G.; Shaw, C.E. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science,  2008, 319(5870), 1668-1672.
[http://dx.doi.org/10.1126/science.1154584] [PMID: 18309045] 
[121] 
Van Den Bosch, L.; Van Damme, P.; Bogaert, E.; Robberecht, W. The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis. Biochim. Biophys. Acta,  2006, 1762(11-12), 1068-1082.
[http://dx.doi.org/10.1016/j.bbadis.2006.05.002] [PMID: 16806844] 
[122] 
Bellingham, M.C. A review of the neural mechanisms of action and clinical efficiency of riluzole in treating amyotrophic lateral sclerosis: What have we learned in the last decade? CNS Neurosci. Ther.,  2011, 17(1), 4-31.
[http://dx.doi.org/10.1111/j.1755-5949.2009.00116.x] [PMID: 20236142] 
[123] 
Inukai, Y.; Nonaka, T.; Arai, T.; Yoshida, M.; Hashizume, Y.; Beach, T.G.; Buratti, E.; Baralle, F.E.; Akiyama, H.; Hisanaga, S.; Hasegawa, M. Abnormal phosphorylation of Ser409/410 of TDP-43 in FTLD-U and ALS. FEBS Lett.,  2008, 582(19), 2899-2904.
[http://dx.doi.org/10.1016/j.febslet.2008.07.027] [PMID: 18656473] 
[124] 
Bissaro, M.; Federico, S.; Salmaso, V.; Sturlese, M.; Spalluto, G.; Moro, S. Targeting protein kinase CK1δ with riluzole: could it be one of the possible missing bricks to interpret its effect in the treatment of ALS from a molecular point of view? ChemMedChem,  2018, 13(24), 2601-2605.
[http://dx.doi.org/10.1002/cmdc.201800632] [PMID: 30359484] 
[125] 
Bissaro, M.; Moro, S. Rethinking to riluzole mechanism of action: the molecular link among protein kinase CK1δ activity, TDP-43 phosphorylation, and amyotrophic lateral sclerosis pharmacological treatment. Neural Regen. Res.,  2019, 14(12), 2083-2085.
[http://dx.doi.org/10.4103/1673-5374.262578] [PMID: 31397342] 
[126] 
Sciabola, S.; Benedetti, P.; D’Arrigo, G.; Torella, R.; Baroni, M.; Cruciani, G.; Spyrakis, F. Discovering new casein kinase 1δ inhibitors with an innovative molecular dynamics enabled virtual screening workflow. ACS Med. Chem. Lett.,  2019, 10(4), 487-492.
[http://dx.doi.org/10.1021/acsmedchemlett.8b00523] [PMID: 30996784] 
[127] 
Shewchuk, L.; Hassell, A.; Wisely, B.; Rocque, W.; Holmes, W.; Veal, J.; Kuyper, L.F. Binding mode of the 4-anilinoquinazoline class of protein kinase inhibitor: X-ray crystallographic studies of 4-anilinoquinazolines bound to cyclin-dependent kinase 2 and p38 kinase. J. Med. Chem.,  2000, 43(1), 133-138.
[http://dx.doi.org/10.1021/jm990401t] [PMID: 10633045] 
[128] 
Karthikeyan, C.; Jharia, P.; Waiker, D.K.; Nusbaum, A.C.; Amawi, H.; Kirwen, E.M.; Christman, R.; Arudra, S.K.C.; Meijer, L.; Tiwari, A.K.; Trivedi, P.N. -(1H-Pyrazol-3-yl)quinazolin-4-amines as a novel class of casein kinase 1δ/ε inhibitors: Synthesis, biological evaluation and molecular modeling studies. Bioorg. Med. Chem. Lett.,  2017, 27(12), 2663-2667.
[http://dx.doi.org/10.1016/j.bmcl.2017.04.080] [PMID: 28487075] 
[129] 
Loidreau, Y.; Marchand, P.; Dubouilh-Benard, C.; Nourrisson, M-R.; Duflos, M.; Lozach, O.; Loaëc, N.; Meijer, L.; Besson, T. Synthesis and biological evaluation of N-arylbenzo[b]thieno[3,2-d]pyrimidin-4-amines and their pyrido and pyrazino analogues as Ser/Thr kinase inhibitors. Eur. J. Med. Chem.,  2012, 58, 171-183.
[http://dx.doi.org/10.1016/j.ejmech.2012.10.006] [PMID: 23124214] 
[130] 
Loidreau, Y.; Deau, E.; Marchand, P.; Nourrisson, M-R.; Logé, C.; Coadou, G.; Loaëc, N.; Meijer, L.; Besson, T. Synthesis and molecular modelling studies of 8-arylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-amines as multitarget Ser/Thr kinases inhibitors. Eur. J. Med. Chem.,  2015, 92, 124-134.
[http://dx.doi.org/10.1016/j.ejmech.2014.12.038] [PMID: 25549552] 
[131] 
Loidreau, Y.; Dubouilh-Benard, C.; Nourrisson, M-R.; Loaëc, N.; Meijer, L.; Besson, T.; Marchand, P. Exploring kinase inhibition properties of 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine derivatives. Pharmaceuticals (Basel),  2020, 13(5), 89.
[http://dx.doi.org/10.3390/ph13050089] [PMID: 32397570] 
[132] 
Park, H.; Jung, H-Y.; Mah, S.; Kim, K.; Hong, S. Kinase and GPCR polypharmacological approach for the identification of efficient anticancer medicines. Org. Biomol. Chem.,  2020, 18(41), 8402-8413.
[http://dx.doi.org/10.1039/D0OB01917H] [PMID: 33112339] 
[133] 
Blunt, J.W.; Copp, B.R.; Keyzers, R.A.; Munro, M.H.G.; Prinsep, M.R. Marine natural products. Nat. Prod. Rep.,  2017, 34(3), 235-294.
[http://dx.doi.org/10.1039/C6NP00124F] [PMID: 28290569] 
[134] 
Kang, H.; Fenical, W. Ningalins A−D: Novel aromatic alkaloids from a western australian ascidian of the genus didemnum. J. Org. Chem.,  1997, 62(10), 3254-3262.
[http://dx.doi.org/10.1021/jo962132+] [PMID: 11671712] 
[135] 
Soenen, D.R.; Hwang, I.; Hedrick, M.P.; Boger, D.L. Multidrug resistance reversal activity of key ningalin analogues. Bioorg. Med. Chem. Lett.,  2003, 13(10), 1777-1781.
[http://dx.doi.org/10.1016/S0960-894X(03)00294-4] [PMID: 12729663] 
[136] 
Plisson, F.; Conte, M.; Khalil, Z.; Huang, X.C.; Piggott, A.M.; Capon, R.J. Kinase inhibitor scaffolds against neurodegenerative diseases from a Southern Australian ascidian, Didemnum sp. ChemMedChem,  2012, 7(6), 983-990.
[http://dx.doi.org/10.1002/cmdc.201200169] [PMID: 22532438] 
[137] 
Baunbaek, D.; Trinkler, N.; Ferandin, Y.; Lozach, O.; Ploypradith, P.; Rucirawat, S.; Ishibashi, F.; Iwao, M.; Meijer, L. Anticancer alkaloid lamellarins inhibit protein kinases. Mar. Drugs,  2008, 6(4), 514-527.
[http://dx.doi.org/10.3390/md20080026] [PMID: 19172192] 
[138] 
Zhang, H.; Xiao, X.; Conte, M.M.; Khalil, Z.; Capon, R.J. Spiralisones A-D: acylphloroglucinol hemiketals from an Australian marine brown alga, Zonaria spiralis. Org. Biomol. Chem.,  2012, 10(48), 9671-9676.
[http://dx.doi.org/10.1039/c2ob26988k] [PMID: 23147836] 
[139] 
Esposito, G.; Bourguet-Kondracki, M.L.; Mai, L.H.; Longeon, A.; Teta, R.; Meijer, L.; Van Soest, R.; Mangoni, A.; Costantino, V. Chloromethylhalicyclamine B, a marine-derived protein kinase CK1δ/ε inhibitor. J. Nat. Prod.,  2016, 79(11), 2953-2960.
[http://dx.doi.org/10.1021/acs.jnatprod.6b00939] [PMID: 27933894] 
[140] 
Gompel, M.; Leost, M.; De Kier Joffe, E.B.; Puricelli, L.; Franco, L.H.; Palermo, J.; Meijer, L. Meridianins, a new family of protein kinase inhibitors isolated from the ascidian Aplidium meridianum. Bioorg. Med. Chem. Lett.,  2004, 14(7), 1703-1707.
[http://dx.doi.org/10.1016/j.bmcl.2004.01.050] [PMID: 15026054] 
[141] 
Akue-Gedu, R.; Debiton, E.; Ferandin, Y.; Meijer, L.; Prudhomme, M.; Anizon, F.; Moreau, P. Synthesis and biological activities of aminopyrimidyl-indoles structurally related to meridianins. Bioorg. Med. Chem.,  2009, 17(13), 4420-4424.
[http://dx.doi.org/10.1016/j.bmc.2009.05.017] [PMID: 19477650] 
[142] 
Llorach-Pares, L.; Nonell-Canals, A.; Sanchez-Martinez, M.; Avila, C. Computer-aided drug design applied to marine drug discovery: Meridianins as Alzheimer’s disease therapeutic agents. Mar. Drugs,  2017, 15(12), 366.
[http://dx.doi.org/10.3390/md15120366] [PMID: 29186912] 
[143] 
Llorach-Pares, L.; Nonell-Canals, A.; Avila, C.; Sanchez-Martinez, M. Kororamides, convolutamines, and indole derivatives as possible tau and dual-specificity kinase inhibitors for Alzheimer’s disease: A computational study. Mar. Drugs,  2018, 16(10), 386.
[http://dx.doi.org/10.3390/md16100386] [PMID: 30332805] 
[144] 
Dashti, Y.; vial, M.L.; Wood, S.A.; Mellick, G.D.; Roullier, C.; Quinn, R.J. Kororamide B. a brominated alkaloid from the bryozoan amathia tortuosa and its effects on Parkinson’s disease cells. Tetrahedron,  2015, 71(41), 7879-7884.
[http://dx.doi.org/10.1016/j.tet.2015.08.017] 
[145] 
Meijer, L.; Thunnissen, A-M.W.H.; White, A.W.; Garnier, M.; Nikolic, M.; Tsai, L-H.; Walter, J.; Cleverley, K.E.; Salinas, P.C.; Wu, Y-Z.; Biernat, J.; Mandelkow, E-M.; Kim, S-H.; Pettit, G.R. Inhibition of cyclin-dependent kinases, GSK-3β and CK1 by hymenialdisine, a marine sponge constituent. Chem. Biol.,  2000, 7(1), 51-63.
[http://dx.doi.org/10.1016/S1074-5521(00)00063-6] [PMID: 10662688] 
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DOI https://dx.doi.org/10.2174/0929867329666220301115124	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Casein Kinase 1δ Inhibitors as Promising Therapeutic Agents for Neurodegenerative Disorders

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