When PERK inhibitors turn out to be new potent RIPK1 inhibitors: Critical issues on the specificity and use of GSK2606414 and GSK2656157

Cell Death and Differentiation

Volumn 24, Issue 6, 2017, Pages 1100-1110

  Rojas Rivera, Diego ^a,b   Delvaeye, Tinneke ^a,b   Roelandt, Ria ^a,b   Nerinckx, Wim ^a,b   Augustyns, Koen ^c   Vandenabeele, Peter ^a,b   Bertrand, Mathieu J M ^a,b  

^a DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^b GHENT UNIVERSITY   (Belgium)

^c UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; CASPASE 3; CASPASE 8; GSK 2606414; GSK 2656157; GSK'963; NECROSTATIN 1S; PHOSPHOTRANSFERASE; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN KINASE RNA LIKE ENDOPLASMIC RETICULUM KINASE; RIPK1 KINASE; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; 7-METHYL-5-(1-((3-(TRIFLUOROMETHYL)PHENYL)ACETYL)-2,3-DIHYDRO-1H-INDOL-5-YL)-7H-PYRROLO(2,3-D)PYRIMIDIN-4-AMINE; ADENINE; EIF2AK3 PROTEIN, HUMAN; GSK2656157; INDOLE DERIVATIVE; PROTEIN KINASE R; RECEPTOR INTERACTING PROTEIN SERINE THREONINE KINASE; RIPK1 PROTEIN, HUMAN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; ARTICLE; AUTOPHOSPHORYLATION; BODY TEMPERATURE; CELL DEATH; CELL PROTECTION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG POTENCY; DRUG POTENTIATION; ENDOPLASMIC RETICULUM STRESS; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INACTIVATION; ENZYME INHIBITION; ENZYME STRUCTURE; FEMALE; GENE ACTIVATION; IC50; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; L929 CELL LINE; LETHALITY; MOLECULAR DOCKING; MOUSE; NECROPTOSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SHOCK; SIGNAL TRANSDUCTION; UNFOLDED PROTEIN RESPONSE; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL LINE; DRUG EFFECTS;

ADENINE; ANIMALS; APOPTOSIS; CELL LINE; EIF-2 KINASE; INDOLES; MICE; RECEPTOR-INTERACTING PROTEIN SERINE-THREONINE KINASES; UNFOLDED PROTEIN RESPONSE;

EID: 85019959498     PISSN: 13509047     EISSN: 14765403     Source Type: Journal    
DOI: 10.1038/cdd.2017.58     Document Type: Article

References (44)

1. Cao SS, Kaufman RJ. Unfolded protein response. Curr Biol 2012; 22: R622-R626.
2. Hetz C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 2012; 13: 89-102.
3. Grootjans J, Kaser A, Kaufman RJ, Blumberg RS. The unfolded protein response in immunity and inflammation. Nat Rev Immunol 2016; 16: 469-484.
4. Cao SS, Luo KL, Shi L. Endoplasmic reticulum stress interacts with inflammation in human diseases. J Cell Physiol 2016; 231: 288-294.
5. Garg AD, Kaczmarek A, Krysko O, Vandenabeele P, Krysko DV, Agostinis P. ER stressinduced inflammation: does it aid or impede disease progression? Trends Mol Med 2012; 18: 589-598.
6. Wang M, Kaufman RJ. The impact of the endoplasmic reticulum protein-folding environment on cancer development. Nat Rev Cancer 2014; 14: 581-597.
7. Tam AB, Mercado EL, Hoffmann A, Niwa M. ER stress activates NF-kappaB by integrating functions of basal IKK activity, IRE1 and PERK. PLoS ONE 2012; 7: e45078.
8. Rutkowski DT, Kaufman RJ. All roads lead to ATF4. Dev Cell 2003; 4: 442-444.
9. Zhang C, Bai N, Chang A, Zhang Z, Yin J, Shen W et al. ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes. Cell Mol Immunol 2013; 10: 84-94.
10. D'Osualdo A, Anania VG, Yu K, Lill JR, Kaufman RJ, Matsuzawa S et al. Transcription factor ATF4 induces NLRP1 inflammasome expression during endoplasmic reticulum stress. PLoS ONE 2015; 10: e0130635.
11. Pakos-Zebrucka K, Koryga I, Mnich K, Ljujic M, Samali A, Gorman AM. The integrated stress response. EMBO Rep 2016; 17: 1374-1395.
12. Hetz C, Chevet E, Harding HP. Targeting the unfolded protein response in disease. Nat Rev Drug Discov 2013; 12: 703-719.
13. Kalliolias GD, Ivashkiv LB. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol 2016; 12: 49-62.
14. Ting AT, Bertrand MJ. More to life than NF-kappaB in TNFR1 signaling. Trends Immunol 2016; 37: 535-545.
15. Pasparakis M, Vandenabeele P. Necroptosis and its role in inflammation. Nature 2015; 517: 311-320.
16. Xue X, Piao JH, Nakajima A, Sakon-Komazawa S, Kojima Y, Mori K et al. Tumor necrosis factor alpha (TNFalpha) induces the unfolded protein response (UPR) in a reactive oxygen species (ROS)-dependent fashion, and the UPR counteracts ROS accumulation by TNFalpha. J Biol Chem 2005; 280: 33917-33925.
17. Masuda M, Miyazaki-Anzai S, Levi M, Ting TC, Miyazaki M. PERK-eIF2alpha-ATF4-CHOP signaling contributes to TNFalpha-induced vascular calcification. J Am Heart Assoc 2013; 2: e000238.
18. Wang L, Du F, Wang X. TNF-alpha induces two distinct caspase-8 activation pathways. Cell 2008; 133: 693-703.
19. Dondelinger Y, Aguileta MA, Goossens V, Dubuisson C, Grootjans S, Dejardin E et al. RIPK3 contributes to TNFR1-mediated RIPK1 kinase-dependent apoptosis in conditions of cIAP1/2 depletion or TAK1 kinase inhibition. Cell Death Differ 2013; 20: 1381-1392.
20. Axten JM, Medina JR, Feng Y, Shu A, Romeril SP, Grant SW et al. Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-p yrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). J Med Chem 2012; 55: 7193-7207.
21. Atkins C, Liu Q, Minthorn E, Zhang SY, Figueroa DJ, Moss K et al. Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res 2013; 73: 1993-2002.
22. Axten JM, Romeril SP, Shu A, Ralph J, Medina JR, Feng Y et al. Discovery of GSK2656157: an optimized PERK inhibitor selected for preclinical development. ACS Med Chem Lett 2013; 4: 964-968.
23. Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 2008; 4: 313-321.
24. Degterev A, Maki JL, Yuan J. Activity and specificity of necrostatin-1, small-molecule inhibitor of RIP1 kinase. Cell Death Differ 2013; 20: 366.
25. Smith AL, Andrews KL, Beckmann H, Bellon SF, Beltran PJ, Booker S et al. Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK). J Med Chem 2015; 58: 1426-1441.
26. Sidrauski C, Acosta-Alvear D, Khoutorsky A, Vedantham P, Hearn BR, Li H et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife 2013; 2: e00498.
27. Harris PA, Bandyopadhyay D, Berger SB, Campobasso N, Capriotti CA, Cox JA et al. Discovery of small molecule RIP1 kinase inhibitors for the treatment of pathologies associated with necroptosis. ACS Med Chem Lett 2013; 4: 1238-1243.
28. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem2010; 31: 455-461.
29. Xie T, Peng W, Liu Y, Yan C, Maki J, Degterev A et al. Structural basis of RIP1 inhibition by necrostatins. Structure 2013; 21: 493-499.
30. Harris PA, King BW, Bandyopadhyay D, Berger SB, Campobasso N, Capriotti CA et al. DNAencoded library screening identifies benzo[b][1,4]oxazepin-4-ones as highly potent and monoselective receptor interacting protein 1 kinase inhibitors. J Med Chem 2016; 59: 2163-2178.
31. Duprez L, Takahashi N, Van Hauwermeiren F, Vandendriessche B, Goossens V, Vanden Berghe T et al. RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome. Immunity 2011; 35: 908-918.
32. Berger SB, Kasparcova V, Hoffman S, Swift B, Dare L, Schaeffer M et al. Cutting Edge: RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPIN-deficient mice. J Immunol 2014; 192: 5476-5480.
33. Takahashi N, Duprez L, Grootjans S, Cauwels A, Nerinckx W, DuHadaway JB et al. Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis 2012; 3: e437.
34. Dondelinger Y, Jouan-Lanhouet S, Divert T, Theatre E, Bertin J, Gough PJ et al. NF-kappaBindependent role of IKKalpha/IKKbeta in preventing RIPK1 kinase-dependent apoptotic and necroptotic cell death during TNF signaling. Mol Cell 2015; 60: 63-76.
35. Berger SB, Harris P, Nagilla R, Kasparcova V, Hoffman S, Swift B et al. Characterization of GSK'963: a structurally distinct, potent and selective inhibitor of RIP1 kinase. Cell Death Discov 2015; 1: 15009.
36. Moreno JA, Halliday M, Molloy C, Radford H, Verity N, Axten JM et al. Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice. Sci Transl Med 2013; 5: 206ra138.
37. Yonekawa T, Gamez G, Kim J, Tan AC, Thorburn J, Gump J et al. RIP1 negatively regulates basal autophagic flux through TFEB to control sensitivity to apoptosis. EMBO Rep 2015; 16: 700-708.
38. Luan Q, Jin L, Jiang CC, Tay KH, Lai F, Liu XY et al. RIPK1 regulates survival of human melanoma cells upon endoplasmic reticulum stress through autophagy. Autophagy 2015; 11: 975-994.
39. Vanlangenakker N, Bertrand MJ, Bogaert P, Vandenabeele P, Vanden Berghe T. TNFinduced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members. Cell Death Dis 2011; 2: e230.
40. Grootjans S, Hassannia B, Delrue I, Goossens V, Wiernicki B, Dondelinger Y et al. A realtime fluorometric method for the simultaneous detection of cell death type and rate. Nat Protoc 2016; 11: 1444-1454.
41. Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 1997; 18: 2714-2723.
42. Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform 2012; 4: 17.
43. Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA. Development and testing of a general amber force field. J Comput Chem 2004; 25: 1157-1174.
44. Sanner MF. Python: a programming language for software integration and development. J Mol Graph Model 1999; 17: 57-61.