Selectivity profiling and biological activity of novel β-carbolines as potent and selective DYRK1 kinase inhibitors

PLoS ONE

Volumn 10, Issue 7, 2015, Pages

  Rüben, Katharina ^a   Wurzlbauer, Anne ^b   Walte, Agnes ^a   Sippl, Wolfgang ^c   Bracher, Franz ^b   Becker, Walter ^a  

^a RWTH AACHEN UNIVERSITY   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

^c MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME A; BETA CARBOLINE; DYRK1 KINASE INHIBITOR; ENZYME INHIBITOR; PLEIOTROPIC PROTEIN KINASE; PROTEIN; PROTEIN KINASE; SEPT4 PROTEIN; SF3B1 PROTEIN; TAU PROTEIN; THREONINE; TYROSINE; UNCLASSIFIED DRUG; CARBOLINE DERIVATIVE; DYRK KINASE; PROTEIN KINASE INHIBITOR; PROTEIN SERINE THREONINE KINASE; PROTEIN TYROSINE KINASE;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ARTICLE; AUTOPHOSPHORYLATION; BIOLOGICAL ACTIVITY; BRAIN DEVELOPMENT; BRAIN FUNCTION; CELL CYCLE REGULATION; CELL VIABILITY; CONTROLLED STUDY; DEGENERATIVE DISEASE; DOWN SYNDROME; MOUSE; NERVE CELL DIFFERENTIATION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; SYNAPTIC TRANSMISSION; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; HELA CELL LINE; HUMAN; METABOLISM; NERVE CELL; PC12 CELL LINE; RAT;

ANIMALS; CARBOLINES; HELA CELLS; HUMANS; NEURONS; PC12 CELLS; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; PROTEIN-TYROSINE KINASES; RATS;

EID: 84941242782     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0132453     Document Type: Article

References (57)

1. Cohen P, Alessi DR. Kinase Drug Discovery-What's Next in the Field? ACS Chem Biol. 2013; 8: 96-104. doi: 10.1021/cb300610s PMID: 23276252
2. Knapp S, Arruda P, Blagg J, Burley S, Drewry DH, Edwards A, et al. A public-private partnership to unlock the untargeted kinome. Nat Chem Biol. 2013; 9: 3-6. doi: 10.1038/nchembio.1113 PMID: 23238671
3. Knight ZA, Shokat KM. Features of selective kinase inhibitors. Chem Biol. 2005; 12: 621-637. PMID: 15975507
4. Cohen P. Guidelines for the effective use of chemical inhibitors of protein function to understand their roles in cell regulation. Biochem J. 2010; 425: 53-54.
5. Frye SV. The art of the chemical probe. Nat Chem Biol. 2010; 6: 159-161. PMID: 20154659
6. Workman P, Collins I. Probing the probes: fitness factors for small molecule tools. Chem Biol. 2010; 17: 561-577. doi: 10.1016/j.chembiol.2010.05.013 PMID: 20609406
7. Lochhead PA, Sibbet G, Morrice N, Cleghon V. Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs. Cell. 2005; 121: 925-36. PMID: 15960979
8. Becker W, Sippl W. Activation, regulation, and inhibition of DYRK1A. FEBS J. 2011; 278: 246-56. doi: 10.1111/j.1742-4658.2010.07956.x PMID: 21126318
9. Walte A, Rüben K, Birner-Gruenberger R, Preisinger C, Bamberg-Lemper S, Hilz N, et al. Mechanism of dual specificity kinase activity of DYRK1A. FEBS J. 2013; 280: 4495-4511. doi: 10.1111/febs.12411 PMID: 23809146
10. Wegiel J, Gong CX, Hwang YW. The role of DYRK1A in neurodegenerative diseases. FEBS J. 2011; 278: 236-245. doi: 10.1111/j.1742-4658.2010.07955.x PMID: 21156028
11. Tejedor FJ, Hämmerle B. MNB/DYRK1A as a multiple regulator of neuronal development. FEBS J. 2011; 278: 223-235. doi: 10.1111/j.1742-4658.2010.07954.x PMID: 21156027
12. Ionescu A, Dufrasne F, Gelbcke M, Jabin I, Kiss R, Lamoral-Theys D. DYRK1A kinase inhibitors with emphasis on cancer. Mini Rev Med Chem. 2012; 12: 1315-1329. PMID: 23016545
13. Smith B, Medda F, Gokhale V, Dunckley T, Hulme C. Recent advances in the design, synthesis, and biological evaluation of selective DYRK1A inhibitors: a new avenue for a disease modifying treatment of Alzheimer's? ACS Chem Neurosci. 2012; 3: 857-872. doi: 10.1021/cn300094k PMID: 23173067
14. Becker W, Soppa U, Tejedor FJ. DYRK1A: a potential drug target for multiple Down syndrome neuropathologies. CNS Neurol Disord Drug Targets. 2014; 13: 26-33. PMID: 24152332
15. Dierssen M. Down syndrome: the brain in trisomic mode. Nat Rev Neurosci. 2012; 13: 844-858. doi: 10.1038/nrn3314 PMID: 23165261
16. Park J, Chung KC. New perspectives of Dyrk1A role in neurogenesis and neuropathologic features of Down syndrome. Exp Neurobiol. 2013; 22: 244-248. doi: 10.5607/en.2013.22.4.244 PMID: 24465139
17. Soppa U, Schumacher J, Florencio Ortiz V, Pasqualon T, Tejedor FJ, Becker W. The Down syndromerelated protein kinase DYRK1A phosphorylates p27(Kip1) and Cyclin D1 and induces cell cycle exit and neuronal differentiation. Cell Cycle. 2014; 13: 2084-2100. doi: 10.4161/cc.29104 PMID: 24806449
18. García-Cerro S, Martínez P, Vidal V, Corrales A, Flórez J, Vidal R, et al. Overexpression of Dyrk1A is implicated in several cognitive, electrophysiological and neuromorphological alterations found in a mouse model of Down syndrome. PLOS ONE 2014; 9: e106572. doi: 10.1371/journal.pone.0106572 PMID: 25188425
19. Ortiz-Abalia J, Sahún I, Altafaj X, Andreu N, Estivill X, Dierssen M, et al. Targeting Dyrk1A with AAVshRNA attenuates motor alterations in TgDyrk1A, a mouse model of Down syndrome. Am J Hum Genet. 2008; 83: 479-488. doi: 10.1016/j.ajhg.2008.09.010 PMID: 18940310
20. De la Torre R, De Sola S, Pons M, Duchon A, de Lagran MM, Farré M, et al. Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans. Mol Nutr Food Res. 2014; 58: 278-288. doi: 10.1002/mnfr.201300325 PMID: 24039182
21. Altafaj X, Martín ED, Ortiz-Abalia J, Valderrama A, Lao-Peregrín C, Dierssen M, et al. Normalization of Dyrk1A expression by AAV2/1-shDyrk1A attenuates hippocampal-dependent defects in the Ts65Dn mouse model of Down syndrome. Neurobiol Dis. 2013; 52: 117-127. doi: 10.1016/j.nbd.2012.11.017 PMID: 23220201
22. Aranda S, Laguna A, de la Luna S. DYRK family of protein kinases: evolutionary relationships, biochemical properties, and functional roles. FASEB J. 2011; 25: 449-462. doi: 10.1096/fj.10-165837 PMID: 21048044
23. Becker W. Emerging role of DYRK family protein kinases as regulators of protein stability in cell cycle control. Cell Cycle 2012; 11: 3389-3394. doi: 10.4161/cc.21404 PMID: 22918246
24. Di Vona C, Bezdan D, Islam AB, Salichs E, López-Bigas N, Ossowski S, et al. Chromatin-wide profiling of DYRK1A reveals a role as a gene-specific RNA polymerase II CTD kinase. Mol Cell 2015; 57: 506-520. doi: 10.1016/j.molcel.2014.12.026 PMID: 25620562
25. Friedman E. Mirk/Dyrk1B in cancer. J Cell Biochem. 2007; 102: 274-279. PMID: 17583556
26. Ashford AL, Oxley D, Kettle J, Hudson K, Guichard S, Cook SJ, et al. A novel DYRK1B inhibitor AZ191 demonstrates that DYRK1B acts independently of GSK3β to phosphorylate cyclin D1 at Thr(286), not Thr(288). Biochem J. 2014; 457: 43-56. doi: 10.1042/BJ20130461 PMID: 24134204
27. Keramati AR, Fathzadeh M, Go GW, Singh R, Choi M, Faramarzi S, et al. A form of the metabolic syndrome associated with mutations in DYRK1B. N Engl J Med. 2014; 370: 1909-1919. doi: 10.1056/NEJMoa1301824 PMID: 24827035
28. Göckler N, Jofre G, Papadopoulos C, Soppa U, Tejedor FJ, Becker W. Harmine specifically inhibits protein kinase DYRK1A and interferes with neurite formation. FEBS J. 2009; 276: 6324-6337. doi: 10.1111/j.1742-4658.2009.07346.x PMID: 19796173
29. Adayev T, Wegiel J, Hwang YW. Harmine is an ATP-competitive inhibitor for dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A). Arch Biochem Biophys. 2011; 507: 212-218. doi: 10.1016/j.abb.2010.12.024 PMID: 21185805
30. Ogawa Y, Nonaka Y, Goto T, Ohnishi E, Hiramatsu T, Kii I. et al. Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A. Nat Commun. 2010; 1: 86. doi: 10.1038/ncomms1090 PMID: 20981014
31. Tahtouh T, Elkins JM, Filippakopoulos P, Soundararajan M, Burgy G, Durieu E, et al. Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B. J. Med. Chem. 2012; 55: 9312-9330. doi: 10.1021/jm301034u PMID: 22998443
32. Ginovart N, Meyer JH, Boovariwala A, Hussey D, Rabiner EA, Houle S, et al. Positron emission tomography quantification of [11C]-harmine binding to monoamine oxidase-A in the human brain. J Cereb Blood Flow Metab. 2006; 26: 330-344. PMID: 16079787
33. Hastie CJ, McLauchlan HJ, Cohen P. Assay of protein kinases using radiolabeled ATP: a protocol. Nat Protoc. 2006; 1: 968-971. PMID: 17406331
34. Drung B, Scholz C, Barbosa VA, Nazari A, Sarragiotto MH, Schmidt B. Computational & experimental evaluation of the structure/activity relationship of β-carbolines as DYRK1A inhibitors. Bioorg Med Chem Lett. 2014; 24: 4854-4860. doi: 10.1016/j.bmcl.2014.08.054 PMID: 25240617
35. Coutadeur S, Benyamine H, Delalonde L, de Oliveira C, Leblond B, Foucourt A, et al. A novel DYRK1A (Dual specificity tyrosine phosphorylation-regulated kinase 1A) inhibitor for the treatment of Alzheimer's disease: effect on Tau and amyloid pathologies in vitro. J. Neurochem. 2015; 133: 440-451. doi: 10.1111/jnc.13018 PMID: 25556849
36. Falke H, Chaikuad A, Becker A, Loaëc N, Lozach O, Abu Jhaisha S, et al. 10-Iodo-11H-indolo[3, 2-c] quinoline-6-carboxylic acids are selective inhibitors of DYRK1A. J Med Chem. 2015; 58:3131-3143. doi: 10.1021/jm501994d PMID: 25730262
37. Schmitt C, Miralinaghi P, Mariano M, Hartmann RW, Engel M. Hydroxybenzothiophene ketones are efficient pre-mRNA splicing modulators due to dual inhibition of Dyrk1A and Clk1/4. ACS Med. Chem. Lett. 2014; 5: 963-7. doi: 10.1021/ml500059y PMID: 25221649
38. Cuny GD, Ulyanova NP, Patnaik D, Liu JF, Lin X, Auerbach K, et al. Structure-activity relationship study of beta-carboline derivatives as haspin kinase inhibitors. Bioorg Med Chem Lett. 2012; 22: 2015-9 doi: 10.1016/j.bmcl.2012.01.028 PMID: 22335895
39. Cuny GD, Robin M, Ulyanova NP, Patnaik D, Pique V, Casano G, et al. Structure-activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors. Bioorg Med Chem Lett. 2010; 20: 3491-3494. PMID: 20836251
40. Eswaran J, Knapp S. Insights into protein kinase regulation and inhibition by large scale structural comparison. Biochim Biophys Acta. 2010; 1804: 429-432. doi: 10.1016/j.bbapap.2009.10.013 PMID: 19854302
41. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, et al. A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J. 2013; 451, 313-28. doi: 10.1042/BJ20121418 PMID: 23398362
42. Dai J, Sultan S, Taylor SS, Higgins JM. The kinase haspin is required for mitotic histone H3 Thr3 phosphorylation and normal metaphase chromosome alignment. Genes Dev. 2005; 19: 472-488. PMID: 15681610
43. Higgins JM. Haspin: a newly discovered regulator of mitotic chromosome behavior. Chromosoma 2010; 119: 137-147. doi: 10.1007/s00412-009-0250-4 PMID: 19997740
44. Graczyk PP. Gini coefficient: a new way to express selectivity of kinase inhibitors against a family of kinases. J Med Chem. 2007; 50: 5773-5779. PMID: 17948979
45. Cozza G, Sarno S, Ruzzene M, Girardi C, Orzeszko A, Kazimierczuk Z, et al. Exploiting the repertoire of CK2 inhibitors to target DYRK and PIM kinases. Biochim Biophys Acta 2013; 1834: 1402-1409. doi: 10.1016/j.bbapap.2013.01.018 PMID: 23360763
46. Huertas D, Soler M, Moreto J, Villanueva A, Martinez A, Vidal A, et al. Antitumor activity of a small-molecule inhibitor of the histone kinase Haspin. Oncogene 2012; 31: 1408-1418. doi: 10.1038/onc.2011. 335 PMID: 21804608
47. Sitz JH, Baumgärtel K, Hämmerle B, Papadopoulos C, Hekerman P, Tejedor FJ, et al. The Down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4. Neuroscience 2008; 157: 596-605. doi: 10.1016/j.neuroscience. 2008.09.034 PMID: 18938227
48. Smyth LA, Collins I. Measuring and interpreting the selectivity of protein kinase inhibitors. J Chem Biol. 2009; 2: 131-151. doi: 10.1007/s12154-009-0023-9 PMID: 19568781
49. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev. 1997; 23: 4-25.
50. Hasegawa K, Yasuda SY, Teo JL, Nguyen C, McMillan M, Hsieh CL, et al. Wnt signaling orchestration with a small molecule DYRK inhibitor provides long-term xeno-free human pluripotent cell expansion. Stem Cells Transl Med. 2012; 1: 18-28. doi: 10.5966/sctm.2011-0033 PMID: 23197636
51. de Graaf K, Czajkowska H, Rottmann S, Packman LC, Lilischkis R, Lüscher B, et al. The protein kinase DYRK1A phosphorylates the splicing factor SF3b1/SAP155 at Thr434, a novel in vivo phosphorylation site. BMC Biochem. 2006; 7: 7. PMID: 16512921
52. Himpel S, Tegge W, Frank R, Leder S, Joost HG, Becker W. Specificity determinants of substrate recognition by the protein kinase DYRK1A. J Biol Chem. 2000; 275: 2431-2438. PMID: 10644696
53. Becker W, Weber Y, Wetzel K, Eirmbter K, Tejedor FJ, Joost HG. Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases. J Biol Chem. 1998; 273: 25893-25902. PMID: 9748265
54. Stefos GC, Soppa U, Dierssen M, Becker W. NGF upregulates the plasminogen activation inhibitor-1 in neurons via the calcineurin/NFAT pathway and the Down syndrome-related proteins DYRK1A and RCAN1 attenuate this effect. PLOS ONE 2013; 8: e67470. doi: 10.1371/journal.pone.0067470 PMID: 23825664
55. Mariano M, Schmitt C, Miralinaghi P, Catto M, Hartmann RW, Carotti A, et al. First selective dual inhibitors of tau phosphorylation and Beta-amyloid aggregation, two major pathogenic mechanisms in Alzheimer's disease. ACS Chem Neurosci. 2014; 5: 1198-1202. doi: 10.1021/cn5001815 PMID: 25247807
56. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, et al. The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007; 408: 297-315. PMID: 17850214
57. Schmitt C, Kail D, Mariano M, Empting M, Weber N, Paul T, et al. Design and synthesis of a library of lead-like 2, 4-bisheterocyclic substituted thiophenes as selective Dyrk/Clk inhibitors. PLOS ONE 2014; 9: e87851. doi: 10.1371/journal.pone.0087851 PMID: 24676346