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Sibiriline, a new small chemical inhibitor of receptor-interacting protein kinase 1, prevents immune-dependent hepatitis

(2017) FEBS JOURNAL. 284(18). p.3050-3068
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Abstract
Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-interacting protein kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a noncommercial, kinase-focused chemical library which allowed us to identify Sibiriline as a new inhibitor of necroptosis induced by tumor necrosis factor (TNF) in Fas-associated protein with death domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis. By using competition binding assay and recombinant kinase assays, we demonstrated that Sib is a rather specific competitive RIPK1 inhibitor. Molecular docking analysis shows that Sib is trapped closed to human RIPK1 adenosine triphosphate-binding site in a relatively hydrophobic pocket locking RIPK1 in an inactive conformation. In agreement with its RIPK1 inhibitory property, Sib inhibits both TNF-induced RIPK1dependent necroptosis and RIPK1-dependent apoptosis. Finally, Sib protects mice from concanavalin A-induced hepatitis. These results reveal the small-molecule Sib as a new RIPK1 inhibitor potentially of interest for the treatment of immune-dependent hepatitis.
Keywords
INFLAMMATORY RESPONSE SYNDROME, MIXED LINEAGE KINASE, INDUCED, LIVER-INJURY, RIP1 KINASE, CELL-DEATH, NONALCOHOLIC STEATOHEPATITIS, NECROPTOSIS INHIBITORS, REGULATED NECROSIS, HIGHLY POTENT, ACTIVATION, Concanavalin A-induced hepatitis, kinase inhibitor, molecular docking, necroptosis, RIPK1 inhibitor

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MLA
Le Cann, Fabienne et al. “Sibiriline, a New Small Chemical Inhibitor of Receptor-interacting Protein Kinase 1, Prevents Immune-dependent Hepatitis.” FEBS JOURNAL 284.18 (2017): 3050–3068. Print.
APA
Le Cann, F., Delehouzé, C., Leverrier-Penna, S., Filliol, A., Comte, A., Delalande, O., Desban, N., et al. (2017). Sibiriline, a new small chemical inhibitor of receptor-interacting protein kinase 1, prevents immune-dependent hepatitis. FEBS JOURNAL, 284(18), 3050–3068.
Chicago author-date
Le Cann, Fabienne, Claire Delehouzé, Sabrina Leverrier-Penna, Aveline Filliol, Arnaud Comte, Olivier Delalande, Nathalie Desban, et al. 2017. “Sibiriline, a New Small Chemical Inhibitor of Receptor-interacting Protein Kinase 1, Prevents Immune-dependent Hepatitis.” Febs Journal 284 (18): 3050–3068.
Chicago author-date (all authors)
Le Cann, Fabienne, Claire Delehouzé, Sabrina Leverrier-Penna, Aveline Filliol, Arnaud Comte, Olivier Delalande, Nathalie Desban, Blandine Baratte, Isabelle Gallais, Claire Piquet-Pellorce, Florence Faurez, Marion Bonnet, Yvette Mettey, Peter Goekjian, Michel Samson, Peter Vandenabeele, Stéphane Bach, and Marie-Thérèse Dimanche-Boitrel. 2017. “Sibiriline, a New Small Chemical Inhibitor of Receptor-interacting Protein Kinase 1, Prevents Immune-dependent Hepatitis.” Febs Journal 284 (18): 3050–3068.
Vancouver
1.
Le Cann F, Delehouzé C, Leverrier-Penna S, Filliol A, Comte A, Delalande O, et al. Sibiriline, a new small chemical inhibitor of receptor-interacting protein kinase 1, prevents immune-dependent hepatitis. FEBS JOURNAL. 2017;284(18):3050–68.
IEEE
[1]
F. Le Cann et al., “Sibiriline, a new small chemical inhibitor of receptor-interacting protein kinase 1, prevents immune-dependent hepatitis,” FEBS JOURNAL, vol. 284, no. 18, pp. 3050–3068, 2017.
@article{8542878,
  abstract     = {Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-interacting protein kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a noncommercial, kinase-focused chemical library which allowed us to identify Sibiriline as a new inhibitor of necroptosis induced by tumor necrosis factor (TNF) in Fas-associated protein with death domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis. By using competition binding assay and recombinant kinase assays, we demonstrated that Sib is a rather specific competitive RIPK1 inhibitor. Molecular docking analysis shows that Sib is trapped closed to human RIPK1 adenosine triphosphate-binding site in a relatively hydrophobic pocket locking RIPK1 in an inactive conformation. In agreement with its RIPK1 inhibitory property, Sib inhibits both TNF-induced RIPK1dependent necroptosis and RIPK1-dependent apoptosis. Finally, Sib protects mice from concanavalin A-induced hepatitis. These results reveal the small-molecule Sib as a new RIPK1 inhibitor potentially of interest for the treatment of immune-dependent hepatitis.},
  author       = {Le Cann, Fabienne and Delehouzé, Claire and Leverrier-Penna, Sabrina and Filliol, Aveline and Comte, Arnaud and Delalande, Olivier and Desban, Nathalie and Baratte, Blandine and Gallais, Isabelle and Piquet-Pellorce, Claire and Faurez, Florence and Bonnet, Marion and Mettey, Yvette and Goekjian, Peter and Samson, Michel and Vandenabeele, Peter and Bach, Stéphane and Dimanche-Boitrel, Marie-Thérèse},
  issn         = {1742-464X},
  journal      = {FEBS JOURNAL},
  keywords     = {INFLAMMATORY RESPONSE SYNDROME,MIXED LINEAGE KINASE,INDUCED,LIVER-INJURY,RIP1 KINASE,CELL-DEATH,NONALCOHOLIC STEATOHEPATITIS,NECROPTOSIS INHIBITORS,REGULATED NECROSIS,HIGHLY POTENT,ACTIVATION,Concanavalin A-induced hepatitis,kinase inhibitor,molecular docking,necroptosis,RIPK1 inhibitor},
  language     = {eng},
  number       = {18},
  pages        = {3050--3068},
  title        = {Sibiriline, a new small chemical inhibitor of receptor-interacting protein kinase 1, prevents immune-dependent hepatitis},
  url          = {http://dx.doi.org/10.1111/febs.14176},
  volume       = {284},
  year         = {2017},
}

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