Achieving effective and selective CK1 inhibitors through structure modification

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1. Rowles J, Slaughter C, Moomaw C, Hsu J, Cobb MH. Purification of casein kinase I and isolation of cDNAs encoding multiple casein kinase I-like enzymes. Proc. Natl Acad. Sci. USA 88, 9548–9552 (1991).
  Medline CASGoogle Scholar
• 2. Knippschild U, Gocht A, Wolff S, Huber N, Lohler J, Stoter M. The casein kinase 1 family: participation in multiple cellular processes in eukaryotes. Cell. Signal. 17(6), 675–689 (2005).
  Medline CASGoogle Scholar
• 3. Gross SD, Anderson RA. Casein kinase I: spatial organization and positioning of a multifunctional protein kinase family. Cell. Signal. 10(10), 699–711 (1998).
  Medline CASGoogle Scholar
• 4. Knippschild U, Wolff S, Giamas G et al. The role of the casein kinase 1 (CK1) family in different signaling pathways linked to cancer development. Onkologie 28(10), 508–514 (2005).
  Medline CASGoogle Scholar
• 5. Budini M, Jacob G, Jedlicki A, Perez C, Allende CC, Allende JE. Autophosphorylation of carboxy-terminal residues inhibits the activity of protein kinase CK1alpha. J. Cell. Biochem. 106(3), 399–408 (2009).
  Medline CASGoogle Scholar
• 6. Dhillon N, Hoekstra MF. Characterization of two protein kinases from Schizosaccharomyces pombe involved in the regulation of DNA repair. EMBO J. 13(12), 2777–2788 (1994).
  Medline CASGoogle Scholar
• 7. Lohler J, Hirner H, Schmidt B et al. Immunohistochemical characterisation of cell-type specific expression of CK1delta in various tissues of young adult BALB/c mice. PLoS ONE 4(1), 12 (2009).
  Google Scholar
• 8. Panchenko MP, Siddiquee Z, Dombkowski DM et al. Protein kinase CK1alphaLS promotes vascular cell proliferation and intimal hyperplasia. Am. J. Pathol. 177(3), 1562–1572 (2010).
  Medline CASGoogle Scholar
• 9. Cheong JK, Nguyen TH, Wang H et al. IC261 induces cell cycle arrest and apoptosis of human cancer cells via CK1δ/ε and Wnt/β-catenin independent inhibition of mitotic spindle formation. Oncogene 30(22), 2558–2569 (2011).
  Medline CASGoogle Scholar
• 10. Meng QJ, Maywood ES, Bechtold DA et al. Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes. Proc. Natl Acad. Sci. USA 107(34), 15240–15245 (2010).
  Medline CASGoogle Scholar
• 11. Curtis AT, Alison JH, Judsen S et al. Small-molecule inhibition of Wnt signaling through activation of casein kinase 1alpha. Nat. Chem. Biol. 6, 829–836 (2010).
  MedlineGoogle Scholar
• 12. Jiang J. CK1 in developmental signaling: Hedgehog and Wnt. Curr. Top. Dev. Biol. 123, 303 (2016).
  MedlineGoogle Scholar
• 13. Niehrs C. The complex world of WNT receptor signalling. Nat. Rev. Mol. Cell Biol. 13(12), 767–779 (2012).
  Medline CASGoogle Scholar
• 14. Cruciat CM. Casein kinase 1 and Wnt/β-catenin signaling. Curr. Opin. Cell Biol. 31, 46–55 (2014).
  Medline CASGoogle Scholar
• 15. Davidson G, Wu W, Shen J et al. Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction. Nature 438(7069), 867–872 (2005).
  Medline CASGoogle Scholar
• 16. Swiatek W, Kang H, Garcia BA et al. Negative regulation of LRP6 function by casein kinase Iepsilon phosphorylation. J. Biol. Chem. 281(18), 12233–12241 (2006).
  Medline CASGoogle Scholar
• 17. Cruciat CM, Niehrs C. Secreted and transmembrane Wnt inhibitors and activators. Cold Spring Harb. Perspect. Biol. 5(3), a015081 (2013).
  MedlineGoogle Scholar
• 18. Meng QJ, Maywood ES, Bechtold DA et al. Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes. Proc. Natl Acad. Sci. USA 24(107), 15240–15245 (2010).
  Google Scholar
• 19. Merrow M, Mazzotta G, Chen Z et al. The right place at the right time: regulation of daily timing by phosphorylation. Genes Dev. 20(19), 2629–2633 (2006).
  Medline CASGoogle Scholar
• 20. Camacho F, Cilio M, Guo Y et al. Human casein kinase I delta phosphorylation of human circadian clock proteins period 1 and 2. FEBS Lett. 489(2–3), 159–165 (2001).
  Medline CASGoogle Scholar
• 21. Lee C, Etchegaray JP, Cagampang RA et al. Posttranslational mechanisms regulate the mammalian circadian clock. Cell 107(7), 855–867 (2001).
  Medline CASGoogle Scholar
• 22. Vielhaber E, Eide E, Rivers A et al. Nuclear entry of the circadian regulator mPER1 is controlled by mammalian casein kinase Iε. Mol. Cell. Biol. 20(13), 4888–4899 (2000).
  Medline CASGoogle Scholar
• 23. Akashi M, Tsuchiya Y, Yoshino T et al. Control of intracellular dynamics of mammalian period proteins by casein kinase 1 epsilon (CK1 epsilon) and CK1delta in cultured cells. Mol. Cell. Biol. 22(6), 1693–1703 (2002).
  Medline CASGoogle Scholar
• 24. Price JL, Blau J, Rothenfluh A et al. Double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation. Cell 94(1), 83–95 (1998).
  Medline CASGoogle Scholar
• 25. Hirota T, Lee JW, Lewis WG et al. High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKIα as a clock regulatory kinase. PLoS Biol. 8(12), 14 (2010).
  Google Scholar
• 26. Li G, Yin H, Kuret J. Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules. J. Biol. Chem. 279(16), 15938–15945 (2004).
  Medline CASGoogle Scholar
• 27. Xu Y, Padiath QS, Shapiro RE et al. Functional consequence of a CK1δ mutation causing familial advanced sleep phase syndrome. Nature 434, 640–644 (2005).
  Medline CASGoogle Scholar
• 28. Yang WS, Stockwell BR. Inhibition of casein kinase 1-epsilon induces cancer-cell-selective, PERIOD2-dependent growth arrest. Genome Biol. 9(6), R92 (2008).
  MedlineGoogle Scholar
• 29. Longenecker KL, Roach PJ, Hurley TD. Three-dimensional structure of mammalian casein kinase I: molecular basis for phosphate recognition. J. Mol. Biol. 257(3), 618–631 (1996).
  Medline CASGoogle Scholar
• 30. Knippschild U, Kruger M, Richter J et al. The CK1 family: contribution to cellular stress response and its role in carcinogenesis. Front. Oncol. 4, 96 (2014).
  MedlineGoogle Scholar
• 31. Xu RM, Carmel G, Sweet RM et al. Crystal structure of casein kinase-1, a phosphate-directed protein kinase. EMBO J. 14(5), 1015–1023 (1995).
  Medline CASGoogle Scholar
• 32. Luxenburger A, Schmidt D, Ianes C et al. Design, synthesis and biological evaluation of isoxazole-based CK1 inhibitors modified with chiral pyrrolidine scaffolds. Molecules 24(5), 873 (2019).
  Google Scholar
• 33. Peifer C, Abadleh M, Bischof J et al. 3,4-diaryl-isoxazoles and -imidazoles as potent dual inhibitors of p38α mitogen activated protein kinase and casein kinase 1δ. J. Med. Chem. 52(23), 7618–7630 (2009).
  Medline CASGoogle Scholar
• 34. Mian A, Schull M, Zhao Z et al. The gatekeeper mutation T315I confers resistance against small molecules by increasing or restoring the ABL-kinase activity accompanied by aberrant transphosphorylation of endogenous BCR, even in loss-of-function mutants of BCR/ABL. Leukemia 23(9), 1614–1621 (2009).
  Medline CASGoogle Scholar
• 35. Rodrigues RP, Da Silva C. Discovery of potential neurodegenerative inhibitors in Alzheimer’s disease by casein kinase 1 structure-based virtual screening. Med. Chem. Res. 26(12), 3274–3285 (2017).
  CASGoogle Scholar
• 36. Flotow H, Graves PR, Wang AQ et al. Phosphate groups as substrate determinants for casein kinase I action. J. Biol. Chem. 265(24), 14264–14269 (1990).
  Medline CASGoogle Scholar
• 37. Roach PJ. Multisite and hierarchal protein phosphorylation. J. Biol. Chem. 266(22), 14139–14142 (1991).
  Medline CASGoogle Scholar
• 38. Marin O, Bustos VH, Cesaro L et al. A noncanonical sequence phosphorylated by casein kinase 1 in beta-catenin may play a role in casein kinase 1 targeting of important signaling proteins. Proc. Natl Acad. Sci. USA 100(18), 10193–10200 (2003).
  Medline CASGoogle Scholar
• 39. Kawakami F, Suzuki K, Ohtsuki K. A novel consensus phosphorylation motif in sulfatide- and cholesterol-3-sulfate-binding protein substrates for CK1 in vitro. Biol. Pharm. Bull. 31(2), 193–200 (2008).
  Medline CASGoogle Scholar
• 40. Gebel J, Tuppi M, Chaikuad A et al. p63 uses a switch-like mechanism to set the threshold for induction of apoptosis. Nat. Chem. Biol 16(10), 1078–1086 (2020).
  Medline CASGoogle Scholar
• 41. Xu RM, Carmel G, Kuret J et al. Structural basis for selectivity of the isoquinoline sulfonamide family of protein kinase inhibitors. Proc. Natl Acad. Sci. USA 93(13), 6308–6313 (1996).
  Medline CASGoogle Scholar
• 42. Chico LK, Van Eldik LJ, Watterson DM. Targeting protein kinases in central nervous system disorders. Nat. Rev. Drug Discov. 8(11), 892–909 (2009).
  Medline CASGoogle Scholar
• 43. Mashhoon N, Demaggio AJ, Tereshko V et al. Crystal structure of a conformation-selective casein kinase-1 inhibitor. J. Biol. Chem. 275(26), 20052–20060 (2000).
  Medline CASGoogle Scholar
• 44. Brockschmidt C, Hirner H, Huber N et al. 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 57(6), 799–806 (2008).
  Medline CASGoogle Scholar
• 45. Fohr KJ, Knippschild U, Herkommer A et al. State-dependent block of voltage-gated sodium channels by the casein-kinase 1 inhibitor IC261. Invest. New Drugs 35(3), 277–289 (2017).
  MedlineGoogle Scholar
• 46. 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. 5(1), 60–65 (2004).
  Medline CASGoogle Scholar
• 47. Bain J, Plater L, Elliott M et al. The selectivity of protein kinase inhibitors: a further update. Biochem. J. 408(3), 297–315 (2007).
  Medline CASGoogle Scholar
• 48. Hu Y, Song W, Cirstea D et al. CSNK1α1 mediates malignant plasma cell survival. Leukemia 29(2), 474–482 (2014).
  MedlineGoogle Scholar
• 49. Badura L, Swanson T, Adamowicz W et al. An inhibitor of casein kinase I epsilon induces phase delays in circadian rhythms under free-running and entrained conditions. J. Pharmacol. Exp. Ther. 322(2), 730–738 (2007). • In this article, the researchers discovered a highly potent and selective CK1ε inhibitor with IC50 value being 7.7 nM. Intensive pharmacology studies were performed to verify the effectiveness. In the free-running animals test, the inhibitor was demonstrated to produce significant phase delay dosing at circadian time.
  Medline CASGoogle Scholar
• 50. Keenan CR, Langenbach SY, Jativa F et al. Casein kinase 1δ/ε inhibitor, PF670462 attenuates the fibrogenic effects of transforming growth factor-β in pulmonary fibrosis. Front. Pharmacol. 9, 738 (2018).
  MedlineGoogle Scholar
• 51. 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. 55(2), 956–960 (2012).
  Medline CASGoogle Scholar
• 52. Walton KM, Fisher K, Rubitski D et al. Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period. J. Pharmacol. Exp. Ther. 330(2), 430–439 (2009).
  Medline CASGoogle Scholar
• 53. Long AM, Zhao H, Huang X. Structural basis for thepotent and selective inhibitionof casein kinase 1 epsilon. J. Med. Chem. 55(22), 10307–10311 (2012). •• Three crystal structures were reported in this article. Based on the in-depth analysis of the molecular mechanism of action, many insights for the design of selective CK1 inhibitors were put forward.
  Medline CASGoogle Scholar
• 54. Graneto MJ, Kurumbail RG, Vazquez ML et al. Synthesis, crystal structure, and activity of pyrazole-based inhibitors of p38 kinase. J. Med. Chem. 50(23), 5712–5719 (2007).
  Medline CASGoogle Scholar
• 55. Mente S, Arnold E, Butler T et al. Ligand-protein interactions of selective casein kinase 1δ inhibitors. J. Med. Chem. 56(17), 6819–6828 (2013).
  Medline CASGoogle Scholar
• 56. Wager TT, Galatsis P, Chandrasekaran RY et al. Identification and profiling of a selective and brain penetrant radioligand for in vivo target occupancy measurement of casein kinase 1 (CK1) inhibitors. ACS Chem. Neurosci. 8(9), 1995–2004 (2017).
  Medline CASGoogle Scholar
• 57. Halekotte J, Witt L, Ianes C et al. Optimized 4,5-diarylimidazoles as potent/selective inhibitors of protein kinase CK1δ and their structural relation to p38αMAPK. Molecules 22(4), 522 (2017).
  Google Scholar
• 58. Schehr M, Ianes C, Weisner J et al. 2-azo-, 2-diazocine-thiazols and 2-azoimidazoles as photoswitchable kinase inhibitors: limitations and pitfalls of the photoswitchable inhibitor approach. Photochem. Photobiol. Sci. 18(6), 1398–1407 (2019).
  Medline CASGoogle Scholar
• 59. Lovering F, Bikker J, Humblet C. Escape from flatland: increasing saturation as an approach to improving clinical success. J. Med. Chem. 52(21), 6752–6756 (2009).
  Medline CASGoogle Scholar
• 60. Huart AS, Saxty B, Merritt A et al. A casein kinase 1/checkpoint kinase 1 pyrazolo-pyridine protein kinase inhibitor as novel activator of the p53 pathway. Bioorg. Med. Chem. Lett. 23(20), 5578–5585 (2013).
  Medline CASGoogle Scholar
• 61. Huang H, Acquaviva L, Berry V et al. Structure-based design of potent and selective CK1γ inhibitors. ACS Med. Chem. Lett. 3(12), 1059–1064 (2012). •• In the field of CK1 inhibitors, few studies were performed on selective CK1γ inhibitors. In this article, structure-based approach was adopted to design a series of highly potent and selectiveCK1γ inhibitors, which exhibit excellent enzyme and cell potency.
  Medline CASGoogle Scholar
• 62. Leban J, Baierl M, Mies J et al. A novel class of potent NF-κB signaling inhibitors. Bioorg. Med. Chem. Lett. 17(21), 5858–5862 (2007).
  Medline CASGoogle Scholar
• 63. Bischof J, Leban J, Zaja M et al. 2-Benzamido-N-(1H-benzo[d]imidazol-2-yl) thiazole-4-carboxamide derivatives as potent inhibitors of CK1δ/ε. Amino Acids 43(4), 1577–1591 (2012).
  Medline CASGoogle Scholar
• 64. Richter J, Bischof J, Zaja M et al. Difluoro-dioxolo-benzoimidazol-benzamides as potent inhibitors of CK1δ and ε with nanomolar inhibitory activity on cancer cell proliferation. J. Med. Chem. 57(19), 7933–7946 (2014). • By analyzing the structure–activity relationship, the researchers designed a series of derivatives with increased biological activity. The preferred compound is inhibitory active and available within the cell.
  Medline CASGoogle Scholar
• 65. Madoux F, Simanski S, Chase P et al. An ultra-high-throughput cell-based screen for wee1 degradation inhibitors. J. Biomol. Screen. 15(8), 907–917 (2010).
  Medline CASGoogle Scholar
• 66. Bibian M, Rahaim RJ, Choi JY et al. Development of highly selective casein kinase 1δ/1ε (CK1δ/ε) inhibitors with potent antiproliferative properties. Bioorg. Med. Chem. Lett. 23(15), 4374–4380 (2013).
  Medline CASGoogle Scholar
• 67. Garcia-Reyes B, Witt L, Jansen B et al. Discovery of inhibitor of wnt production 2 (IWP-2) and related compounds as selective ATP-competitive inhibitors of casein kinase 1 (CK1) δ /ε. J. Med. Chem. 61(9), 4087–4102 (2018).
  Medline CASGoogle Scholar
• 68. Salado IG, Redondo M, Bello ML et al. Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis. J. Med. Chem. 57(6), 2755–2772 (2014). • By the approach of chemical genetic, the researchers discovered and optimized several CK1 inhibitors. In the cell assay, these compounds were able to exhibit inhibitory effects. Thus, the molecules are hopeful tools to study the therapy of ALS.
  Medline CASGoogle Scholar
• 69. Lee JW, Hirota T, Peters EC et al. A small molecule modulates circadian rhythms through phosphorylation of the period protein. Angew Chem. Int. Ed. Engl. 50(45), 10608–10611 (2011).
  Medline CASGoogle Scholar
• 70. Etchegaray JP, Machida KK, Noton E et al. Casein kinase 1 delta regulates the pace of the mammalian circadian clock. Mol. Cell. Biol. 29(14), 3853–3866 (2009).
  Medline CASGoogle Scholar
• 71. Miyazaki K, Nagase T, Mesaki M et al. Phosphorylation of clock protein PER1 regulates its circadian degradation in normal human fibroblasts. Biochem. J. 380(Pt 1), 95–103 (2004).
  Medline CASGoogle Scholar
• 72. Lee JW, Hirota T, Ono D et al. Chemical control of mammalian circadian behavior through dual inhibition of casein kinase Iα and δ. J. Med. Chem. 62(4), 1989–1998 (2019).
  Medline CASGoogle Scholar
• 73. Yang LL, Li GB, Yan HX et al. Discovery of N6-phenyl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamine derivatives as novel CK1 inhibitors using common-feature pharmacophore model based virtual screening and hit-to-lead optimization. Eur. J. Med. Chem. 56, 30–38 (2012).
  Medline CASGoogle Scholar
• 74. Lee MR, Dominguez C. MAP kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38 protein. Curr. Med. Chem. 12(25), 2979–2994 (2005).
  Medline CASGoogle Scholar
• 75. Miwatashi S, Arikawa Y, Kotani E et al. Novel inhibitor of p38 MAP kinase as an anti-TNF-α drug: discovery of N-[4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (TAK-715) as a potent and orally active anti-rheumatoid arthritis agent. J. Med. Chem. 48(19), 5966–5979 (2005).
  Medline CASGoogle Scholar
• 76. Verkaar F, Van Der Doelen AA, Smits JF, Blankesteijn WM, Zaman GJ. Inhibition of Wnt/β-catenin signaling by p38 MAP kinase inhibitors is explained by cross-reactivity with casein kinase Iδ/ε. Chem. Biol. 18(4), 485–494 (2011).
  Medline CASGoogle Scholar
• 77. Myrianthopoulos V, Lozach O, Zareifi D et al. Combined virtual and experimental screening for CK1 inhibitors identifies a modulator of p53 and reveals important aspects of in silico screening performance. Int. J. Mol. Sci. 18(10), 2102 (2017).
  Google Scholar
• 78. List A, Dewald G, Bennett J et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N. Engl. J. Med. 355(14), 1456–1465 (2006).
  Medline CASGoogle Scholar
• 79. Kronke J, Fink EC, Hollenbach PW et al. Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS. Nature 523(7559), 183–188 (2015).
  Medline CASGoogle Scholar
• 80. Petzold G, Fischer ES, Thoma NH. Structrual basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase. Nature 532(7597), 127–130 (2016). •• In the research field of CK1, protein–protein interaction are rarely mentioned. In this article, the author reported the crystal structure of DDB1–CRBN bound to lenalidomide and CK1α, providing novel ideas for future drug design.
  Medline CASGoogle Scholar
• 81. Yang Y, Shaffer Arthur L, Emre NCT et al. Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell 21(6), 723–737 (2012).
  Medline CASGoogle Scholar
• 82. Minzel W, Venkatachalam A, Flink A et al. Small molecules co-targeting CK1α and the transcriptional kinase CDK7/9 control AML in preclinical models. Cell 175(1), 171–185 (2018).
  Medline CASGoogle Scholar
• 83. Kojima K, Ishizawa J, Andreeff M. Pharmacological activation of wild-type p53 in the therapy of leukemia. Exp. Hematol. 44(9), 791–798 (2016).
  Medline CASGoogle Scholar
• 84. Klaeger S, Heinzlmeir S, Wilhelm M et al. The target landscape of clinical kinase drugs. Science 358(6367), eaan4368 (2017).
  MedlineGoogle Scholar