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ATP site-directed inhibitors of protein kinase CK2: an update.

Sarno S, Papinutto E, Franchin C, Bain J, Elliott M, Meggio F, Kazimierczuk Z, Orzeszko A, Zanotti G, Battistutta R, Pinna LA
Curr Top Med Chem 11 1340-51 (2011)
Related entries: 1zoe, 1zog, 1zoh, 2oxd, 2oxx, 2oxy, 3kxg, 3kxh, 3kxn, 3pvg

Cited: 49 times
EuropePMC logo PMID: 21513497

Abstract

CK2 denotes a pleiotropic, constitutively active protein kinase whose abnormally high level in many cancer cells is held as an example of "non oncogene addiction". A wide spectrum of cell permeable, fairly specific ATP site-directed CK2 inhibitors are currently available which are proving useful to dissect its biological functions and which share the property of inducing apoptosis of cancer cells with no comparable effect on their "normal" counterparts. One of these, CX-4945, has recently entered clinical trials for the treatment of advanced solid tumors, Castelman's disease and multiple myeloma. The solution of a wide range of 3D structures of inhibitors bound to the catalytic subunits of CK2 reveals that their efficacy substantially relies on hydrophobic interactions within a cavity which is smaller than in other protein kinases. Accordingly the potency of tetra-halogenated benzimidazoles increases upon replacement of chlorine by bromine and, even more, by iodine, and decreases if two unique bulky side chains on CK2 (Val66 and Ile174) are mutated to alanines. Many CK2 inhibitors have been tested on a panel of more than 60 kinases providing Promiscuity Scores useful to evaluate their selectivity, the lowest value (9.47), denoting highest selectivity, being displayed by quinalizarin. The observation that CK2 inhibitors with medium/high promiscuity scores share the ability to inhibit a group of protein kinases as effectively as CK2 discloses the possibility of using their scaffolds for the rational development of selective inhibitors of these kinases, with special reference to PIMs, DYRKs, HIPK2, PKD and ERK8.

Reviews - 3kxm mentioned but not cited (1)

  1. The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design. Cozza G. Pharmaceuticals (Basel) 10 E26 (2017)


Reviews citing this publication (8)

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Articles citing this publication (40)

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  4. Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2. Guillon J, Le Borgne M, Rimbault C, Moreau S, Savrimoutou S, Pinaud N, Baratin S, Marchivie M, Roche S, Bollacke A, Pecci A, Alvarez L, Desplat V, Jose J. Eur J Med Chem 65 205-222 (2013)
  5. The Thr205 phosphorylation site within respiratory syncytial virus matrix (M) protein modulates M oligomerization and virus production. Bajorek M, Caly L, Tran KC, Maertens GN, Tripp RA, Bacharach E, Teng MN, Ghildyal R, Jans DA. J. Virol. 88 6380-6393 (2014)
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  7. Synthesis, Biological Evaluation and Molecular Modeling of Substituted Indeno[1,2-b]indoles as Inhibitors of Human Protein Kinase CK2. Alchab F, Ettouati L, Bouaziz Z, Bollacke A, Delcros JG, Gertzen CG, Gohlke H, Pinaud N, Marchivie M, Guillon J, Fenet B, Jose J, Borgne ML. Pharmaceuticals (Basel) 8 279-302 (2015)
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  10. PML Degradation: Multiple Ways to Eliminate PML. Rabellino A, Scaglioni PP. Front Oncol 3 60 (2013)
  11. Exploiting the repertoire of CK2 inhibitors to target DYRK and PIM kinases. Cozza G, Sarno S, Ruzzene M, Girardi C, Orzeszko A, Kazimierczuk Z, Zagotto G, Bonaiuto E, Di Paolo ML, Pinna LA. Biochim. Biophys. Acta 1834 1402-1409 (2013)
  12. The protein kinase 2 inhibitor CX-4945 regulates osteoclast and osteoblast differentiation in vitro. Son YH, Moon SH, Kim J. Mol. Cells 36 417-423 (2013)
  13. Functional proteomics strategy for validation of protein kinase inhibitors reveals new targets for a TBB-derived inhibitor of protein kinase CK2. Gyenis L, Kuś A, Bretner M, Litchfield DW. J Proteomics 81 70-79 (2013)
  14. Halogen bonding at the ATP binding site of protein kinases: preferred geometry and topology of ligand binding. Poznański J, Shugar D. Biochim. Biophys. Acta 1834 1381-1386 (2013)
  15. Different Persistence of the Cellular Effects Promoted by Protein Kinase CK2 Inhibitors CX-4945 and TDB. Girardi C, Ottaviani D, Pinna LA, Ruzzene M. Biomed Res Int 2015 185736 (2015)
  16. Discovery and characterization of synthetic 4'-hydroxyflavones-New CK2 inhibitors from flavone family. Golub AG, Bdzhola VG, Ostrynska OV, Kyshenia IV, Sapelkin VM, Prykhod'ko AO, Kukharenko OP, Yarmoluk SM. Bioorg. Med. Chem. 21 6681-6689 (2013)
  17. Structural basis for low-affinity binding of non-R2 carboxylate-substituted tricyclic quinoline analogs to CK2α: comparative molecular dynamics simulation studies. Zhou Y, Li X, Zhang N, Zhong R. Chem Biol Drug Des 85 189-200 (2015)
  18. Structure and Property Based Design of Pyrazolo[1,5-a]pyrimidine Inhibitors of CK2 Kinase with Activity in Vivo. Dowling JE, Alimzhanov M, Bao L, Block MH, Chuaqui C, Cooke EL, Denz CR, Hird A, Huang S, Larsen NA, Peng B, Pontz TW, Rivard-Costa C, Saeh JC, Thakur K, Ye Q, Zhang T, Lyne PD. ACS Med Chem Lett 4 800-805 (2013)
  19. Halogen Atoms in the Protein-Ligand System. Structural and Thermodynamic Studies of the Binding of Bromobenzotriazoles by the Catalytic Subunit of Human Protein Kinase CK2. Czapinska H, Winiewska-Szajewska M, Szymaniec-Rutkowska A, Piasecka A, Bochtler M, Poznański J. J Phys Chem B 125 2491-2503 (2021)
  20. Protein Kinase CK2 Expression Predicts Relapse Survival in ERα Dependent Breast Cancer, and Modulates ERα Expression in Vitro. Williams MD, Nguyen T, Carriere PP, Tilghman SL, Williams C. Int J Environ Res Public Health 13 ijerph13010036 (2015)
  21. Synthesis and properties of a selective inhibitor of homeodomain-interacting protein kinase 2 (HIPK2). Cozza G, Zanin S, Determann R, Ruzzene M, Kunick C, Pinna LA. PLoS ONE 9 e89176 (2014)
  22. In Search of Small Molecule Inhibitors Targeting the Flexible CK2 Subunit Interface. Bestgen B, Belaid-Choucair Z, Lomberget T, Le Borgne M, Filhol O, Cochet C. Pharmaceuticals (Basel) 10 (2017)
  23. Inhibition of casein kinase 2 prevents growth of human osteosarcoma. Takahashi K, Setoguchi T, Tsuru A, Saitoh Y, Nagano S, Ishidou Y, Maeda S, Furukawa T, Komiya S. Oncol. Rep. 37 1141-1147 (2017)
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  25. Toward selective CK2alpha and CK2alpha' inhibitors: Development of a novel whole-cell kinase assay by Autodisplay of catalytic CK2alpha'. Bollacke A, Nienberg C, Borgne ML, Jose J. J Pharm Biomed Anal 121 253-260 (2016)
  26. Benzimidazole inhibitors of protein kinase CK2 potently inhibit the activity of atypical protein kinase Rio1. Kubiński K, Masłyk M, Orzeszko A. Mol. Cell. Biochem. 426 195-203 (2017)
  27. Exploring the Activity of Fungal Phenalenone Derivatives as Potential CK2 Inhibitors Using Computational Methods. Ibrahim SRM, Bagalagel AA, Diri RM, Noor AO, Bakhsh HT, Muhammad YA, Mohamed GA, Omar AM. J Fungi (Basel) 8 443 (2022)
  28. ROCK2-Specific Inhibitor KD025 Suppresses Adipocyte Differentiation by Inhibiting Casein Kinase 2. Tran NNQ, Chun KH. Molecules 26 4747 (2021)
  29. Screening of tau protein kinase inhibitors in a tauopathy-relevant cell-based model of tau hyperphosphorylation and oligomerization. Yadikar H, Torres I, Aiello G, Kurup M, Yang Z, Lin F, Kobeissy F, Yost R, Wang KK. PLoS One 15 e0224952 (2020)
  30. Exploring the Pivotal Role of the CK2 Hinge Region Sub-Pocket in Binding with Tricyclic Quinolone Analogues by Computational Analysis. Zhou Y, Zhang N, Tang S, Qi X, Zhao L, Zhong R, Peng Y. Molecules 22 (2017)
  31. Involvement of endothelial CK2 in the radiation induced perivascular resistant niche (PVRN) and the induction of radioresistance for non-small cell lung cancer (NSCLC) cells. Li Q, Zong Y, Li K, Jie X, Hong J, Zhou X, Wu B, Li Z, Zhang S, Wu G, Meng R. Biol. Res. 52 22 (2019)
  32. Synthesis and Crystal Structure of Adamantylated 4,5,6,7-Tetrahalogeno-1H-benzimidazoles Novel Multi-Target Ligands (Potential CK2, M2 and SARS-CoV-2 Inhibitors); X-ray/DFT/QTAIM/Hirshfeld Surfaces/Molecular Docking Study. Latosińska JN, Latosińska M, Orzeszko A, Maurin JK. Molecules 28 147 (2022)
  33. Synthesis of Novel Halogenated Heterocycles Based on o-Phenylenediamine and Their Interactions with the Catalytic Subunit of Protein Kinase CK2. Winiewska-Szajewska M, Maciejewska AM, Speina E, Poznański J, Paprocki D. Molecules 26 3163 (2021)
  34. The crystal structure of the protein kinase HIPK2 reveals a unique architecture of its CMGC-insert region. Agnew C, Liu L, Liu S, Xu W, You L, Yeung W, Kannan N, Jablons D, Jura N. J. Biol. Chem. 294 13545-13559 (2019)
  35. CIGB-300-Regulated Proteome Reveals Common and Tailored Response Patterns of AML Cells to CK2 Inhibition. Rosales M, Rodríguez-Ulloa A, Pérez GV, Besada V, Soto T, Ramos Y, González LJ, Zettl K, Wiśniewski JR, Yang K, Perera Y, Perea SE. Front Mol Biosci 9 834814 (2022)
  36. Crystal structure of Arabidopsis thaliana casein kinase 2 α1. Demulder M, De Veylder L, Loris R. Acta Crystallogr F Struct Biol Commun 76 182-191 (2020)
  37. Insights into the Impact of Linker Flexibility and Fragment Ionization on the Design of CK2 Allosteric Inhibitors: Comparative Molecular Dynamics Simulation Studies. Zhou Y, Zhang N, Qi X, Tang S, Sun G, Zhao L, Zhong R, Peng Y. Int J Mol Sci 19 (2018)
  38. Mechanism of CK2 Inhibition by a Ruthenium-Based Polyoxometalate. Fabbian S, Giachin G, Bellanda M, Borgo C, Ruzzene M, Spuri G, Campofelice A, Veneziano L, Bonchio M, Carraro M, Battistutta R. Front Mol Biosci 9 906390 (2022)
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  40. Unexpected Binding Mode of a Potent Indeno[1,2-b]indole-Type Inhibitor of Protein Kinase CK2 Revealed by Complex Structures with the Catalytic Subunit CK2α and Its Paralog CK2α'. Hochscherf J, Lindenblatt D, Witulski B, Birus R, Aichele D, Marminon C, Bouaziz Z, Le Borgne M, Jose J, Niefind K. Pharmaceuticals (Basel) 10 (2017)


Related citations provided by authors (2)

  1. Inspecting the structure-activity relationship of protein kinase CK2 inhibitors derived from tetrabromo-benzimidazole.. Battistutta R, Mazzorana M, Sarno S, Kazimierczuk Z, Zanotti G, Pinna LA Chem Biol 12 1211-9 (2005)
  2. The ATP-binding site of protein kinase CK2 holds a positive electrostatic area and conserved water molecules.. Battistutta R, Mazzorana M, Cendron L, Bortolato A, Sarno S, Kazimierczuk Z, Zanotti G, Moro S, Pinna LA Chembiochem 8 1804-9 (2007)

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