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Review

Necroptosis inhibitors as therapeutic targets in inflammation mediated disorders - a review of the current literature and patents

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Pages 1239-1256 | Received 14 Jun 2016, Accepted 25 Aug 2016, Published online: 08 Sep 2016

References

  • Opferman JT, Korsmeyer SJ. Apoptosis in the development and maintenance of the immune system. Nat Immunol. 2003;4(5):410–415. [Epub 2003 Apr 30].
  • Degterev A, Yuan J. Expansion and evolution of cell death programmes. Nat Rev Mol Cell Biol. 2008;9(5):378–390. [Epub 2008 Apr 17].
  • Lockshin RA. Programmed cell death 50 (and beyond). Cell Death Differ. 2016;23:10–17.
  • Majno G, Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol. 1995;146(1):3–15.
  • Kroemer G, Galluzzi L, Vandenabeele P, et al. Classification of cell death: recommendations of the nomenclature committee on cell death 2009. Cell Death Differ. 2009;16(1):3–11. [Epub 2008 Oct 11].
  • Linkermann A, Green DR. Necroptosis. N Engl J Med. 2014;370(5):455–465. [Epub 2014 Jan 31]
  • Chan FK, Luz NF, Moriwaki K. Programmed necrosis in the cross talk of cell death and inflammation. Annu Rev Immunol. 2015;33:79–106. [Epub 2014 Dec 11].
  • Christofferson DE, Li Y, Yuan J. Control of life-or-death decisions by RIP1 kinase. Annu Rev Physiol. 2014;76:129–150. [Epub 2013 Oct 2].
  • Nikoletopoulou V, Markaki M, Palikaras K, et al. Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta. 2013;1833(12):3448–3459. [Epub 2013 Jun 19].
  • Wu W, Liu P, Li J. Necroptosis: an emerging form of programmed cell death. Crit Rev Oncol Hematol. 2012;82(3):249–258. [Epub 2011 Oct 4].
  • Laster SM, Wood JG, Gooding LR. Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis. J Immunol. 1988;141(8):2629–2634. [Epub 1988 Oct 15].
  • Vercammen D, Beyaert R, Denecker G, et al. Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor. J Exp Med. 1998;187(9):1477–1485. [Epub 1998 June 6].
  • Holler N, Zaru R, Micheau O, et al. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol. 2000;1(6):489–495. [Epub 2001 Mar 23].
  • Lin Y, Choksi S, Shen HM, et al. Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation. J Biol Chem. 2004;279(11):10822–10828. [Epub 2004 Jan 1].
  • Cho YS, Challa S, Moquin D, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009;137(6):1112–1123. [Epub 2009 Jun 16].
  • He S, Wang L, Miao L, et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-α. Cell. 2009;137(6):1100–1111. [Epub 2009 Jun 16].
  • Zhang DW, Shao J, Lin J, et al. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science. 2009;325(5938):332–336. [Epub 2009 Jun 06].
  • Wallach D. Cell death induction by TNF: a matter of self control. Trends Biochem Sci. 1997;22(4):107–109. [Epub 1997 Apr 1].
  • Pennarun B, Meijer A, de Vries EG, et al. Playing the DISC: turning on TRAIL death receptor-mediated apoptosis in cancer. Biochim Biophys Acta. 2010;1805(2):123–140. [Epub 2009 Dec 8].
  • Fiers W, Beyaert R, Declercq W, et al. More than one way to die: apoptosis, necrosis and reactive oxygen damage. Oncogene. 1999;18(54):7719–7730. [Epub 2000 Jan 5].
  • Chan FK, Shisler J, Bixby JG, et al. A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses. J Biol Chem. 2003;278(51):51613–51621. [Epub 2003 Oct 9].
  • Jouan-Lanhouet S, Arshad MI, Piquet-Pellorce C, et al. TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation. Cell Death Differ. 2012;19(12):2003–2014. [Epub 2012 July 21].
  • Duprez L, Takahashi N, Van Hauwermeiren F, et al. RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome. Immunity. 2011;35(6):908–918. [Epub 2011 Dec 27].
  • Linkermann A, Brasen JH, Darding M, et al. Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury. Proc Natl Acad Sci USA. 2013;110(29):12024–12029. [Epub 2013 Jul 3].
  • Feoktistova M, Geserick P, Kellert B, et al. cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Mol Cell. 2011;43(3):449–463. [Epub 2011 Jul 9].
  • Upton JW, Kaiser WJ, Mocarski ES. Virus inhibition of RIP3-dependent necrosis. Cell Host Microbe. 2010;7(4):302–313. [Epub 2010 Apr 24].
  • Martinon F, Gaide O, Petrilli V, et al. NALP inflammasomes: a central role in innate immunity. Semin Immunopathol. 2007;29(3):213–229. [Epub 2007 Aug 19].
  • Kalai M, Van Loo G, Vanden Berghe T, et al. Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA. Cell Death Differ. 2002;9(9):981–994. [Epub 2002 Aug 16].
  • Matsumura H, Shimizu Y, Ohsawa Y, et al. Necrotic death pathway in Fas receptor signaling. J Cell Biol. 2000;151(6):1247–1256. [Epub 2000 Dec 21].
  • Vercammen D, Brouckaert G, Denecker G, et al. Dual signaling of the Fas receptor: initiation of both apoptotic and necrotic cell death pathways. J Exp Med. 1998;188(5):919–930. [Epub 1998 Sept 9].
  • Fulda S. The mechanism of necroptosis in normal and cancer cells. Cancer Biol Ther. 2013;14(11):999–1004. [Epub 2013 Sept 13].
  • Christofferson DE, Yuan J. Necroptosis as an alternative form of programmed cell death. Curr Opin Cell Biol. 2010;22(2):263–268. [Epub 2010 Jan 5].
  • Cho Y, McQuade T, Zhang H, et al. RIP1-dependent and independent effects of necrostatin-1 in necrosis and T cell activation. PLoS One. 2011;6(8):e23209. [Epub 2011 Aug 20].
  • Kaiser WJ, Upton JW, Mocarski ES. Viral modulation of programmed necrosis. Curr Opin Virol. 2013;3(3):296–306. [Epub 2013 Jun 19].
  • Degterev A, Hitomi J, Germscheid M, et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol. 2008;4(5):313–321. [Epub 2008 Apr 15].
  • Smith CC, Davidson SM, Lim SY, et al. Necrostatin: a potentially novel cardioprotective agent? Cardiovasc Drugs Ther. 2007;21(4):227–233. [Epub 2007 Aug 1].
  • Lin J, Li H, Yang M, et al. A role of RIP3-mediated macrophage necrosis in atherosclerosis development. Cell Rep. 2013;3(1):200–210. [Epub 2013 Jan 22].
  • Linkermann A, Brasen JH, Himmerkus N, et al. Rip1 (receptor-interacting protein kinase 1) mediates necroptosis and contributes to renal ischemia/reperfusion injury. Kidney Int. 2012;81(8):751–761. [Epub 2012 Jan 13].
  • Oerlemans MI, Liu J, Arslan F, et al. Inhibition of RIP1-dependent necrosis prevents adverse cardiac remodeling after myocardial ischemia-reperfusion in vivo. Basic Res Cardiol. 2012;107(4):270. [Epub 2012 May 4].
  • Wu J, Huang Z, Ren J, et al. Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis. Cell Res. 2013;23(8):994–1006. [Epub 2013 Jul 10].
  • Gunther C, Martini E, Wittkopf N, et al. Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis. Nature. 2011;477(7364):335–339. [Epub 2011 Sep 17].
  • Welz PS, Wullaert A, Vlantis K, et al. FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature. 2011;477(7364):330–334. [Epub 2011 Aug 2].
  • Re DB, Le Verche V, Yu C, et al. Necroptosis drives motor neuron death in models of both sporadic and familial ALS. Neuron. 2014;81(5):1001–1008. [Epub 2014 Feb 11].
  • Zhu S, Zhang Y, Bai G, et al. Necrostatin-1 ameliorates symptoms in R6/2 transgenic mouse model of Huntington’s disease. Cell Death Dis. 2011;2:e115. [Epub 2011 Mar 2].
  • Xu X, Chua CC, Kong J, et al. Necrostatin-1 protects against glutamate-induced glutathione depletion and caspase-independent cell death in HT-22 cells. J Neurochem. 2007;103(5):2004–2014. [Epub 2007 Sep 1].
  • Li Y, Yang X, Ma C, et al. Necroptosis contributes to the NMDA-induced excitotoxicity in rat’s cultured cortical neurons. Neurosci Lett. 2008;447(2–3):120–123. [Epub 2008 Aug 30].
  • Yamanaka K, Saito Y, Yamamori T, et al. 24(S)-hydroxycholesterol induces neuronal cell death through necroptosis, a form of programmed necrosis. J Biol Chem. 2011;286(28):24666–24673. [Epub 2011 May 27].
  • Rock KL, Latz E, Ontiveros F, et al. The sterile inflammatory response. Annu Rev Immunol. 2010;28:321–342.
  • Linkermann A, Stockwell BR, Krautwald S, et al. Regulated cell death and inflammation: an auto-amplification loop causes organ failure. Nat Rev Immunol. 2014;14(11):759–767.
  • Wallach D, Kang TB, Kovalenko A. Concepts of tissue injury and cell death in inflammation: a historical perspective. Nat Rev Immunol. 2014;14(1):51–59. [Epub 2013 Dec 18].
  • Kim SK, Kim WJ, Yoon JH, et al. Upregulated RIP3 expression potentiates MLKL phosphorylation-mediated programmed necrosis in toxic epidermal necrolysis. J Invest Dermatol. 2015;135(8):2021–2030. [Epub 2015 Mar 10].
  • Ofengeim D, Ito Y, Najafov A, et al. Activation of necroptosis in multiple sclerosis. Cell Rep. 2015;10(11):1836–1849. [Epub 2015 Mar 25].
  • Christofferson DE, Li Y, Hitomi J, et al. A novel role for RIP1 kinase in mediating TNFα production. Cell Death Dis. 2012;3:e320. [Epub 2012 Jun 15].
  • Wang H, Sun L, Su L, et al. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell. 2014;54(1):133–146. [Epub 2014 Apr 8].
  • Murakami Y, Matsumoto H, Roh M, et al. Programmed necrosis, not apoptosis, is a key mediator of cell loss and DAMP-mediated inflammation in dsRNA-induced retinal degeneration. Cell Death Differ. 2014;21(2):270–277. [Epub 2013 Aug 21].
  • Sharma A, Matsuo S, Yang WL, et al. Receptor-interacting protein kinase 3 deficiency inhibits immune cell infiltration and attenuates organ injury in sepsis. Crit Care. 2014;18(4):R142. [Epub 2014 Jul 6].
  • Vitner EB, Salomon R, Farfel-Becker T, et al. RIPK3 as a potential therapeutic target for Gaucher’s disease. Nat Med. 2014;20(2):204–208. [Epub 2014 Jan 21].
  • Degterev A, Huang Z, Boyce M, et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 2005;1(2):112–119. [Epub 2006 Jan 13].
  • Artal-Sanz M, Tavernarakis N. Proteolytic mechanisms in necrotic cell death and neurodegeneration. FEBS Lett. 2005;579(15):3287–3296. [Epub 2005 Jun 10].
  • Brouckaert G, Kalai M, Krysko DV, et al. Phagocytosis of necrotic cells by macrophages is phosphatidylserine dependent and does not induce inflammatory cytokine production. Mol Biol Cell. 2004;15(3):1089–1100. [Epub 2003 Dec 12].
  • Vandenabeele P, Galluzzi L, Vanden Berghe T, et al. Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol. 2010;11(10):700–714. [Epub 2010 Sep 9].
  • Wang K, Li J, Degterev A, et al. Structure-activity relationship analysis of a novel necroptosis inhibitor, Necrostatin-5. Bioorg Med Chem Lett. 2007;17(5):1455–1465. [Epub 2007 Feb 3].
  • Teng X, Degterev A, Jagtap P, et al. Structure-activity relationship study of novel necroptosis inhibitors. Bioorg Med Chem Lett. 2005;15(22):5039–5044. [Epub 2005 Sep 13].
  • Teng X, Keys H, Jeevanandam A, et al. Structure-activity relationship study of [1,2,3]thiadiazole necroptosis inhibitors. Bioorg Med Chem Lett. 2007;17(24):6836–6840. [Epub 2007 Oct 30].
  • Jagtap PG, Degterev A, Choi S, et al. Structure-activity relationship study of tricyclic necroptosis inhibitors. J Med Chem. 2007;50(8):1886–1895. [Epub 2007 Mar 17].
  • Xie T, Peng W, Liu Y, et al. Structural basis of RIP1 inhibition by necrostatins. Structure. 2013;21(3):493–499.
  • Rosenbaum DM, Degterev A, David J, et al. Necroptosis, a novel form of caspase-independent cell death, contributes to neuronal damage in a retinal ischemia-reperfusion injury model. J Neurosci Res. 2010;88(7):1569–1576. [Epub 2009 Dec 22].
  • Lim SY, Davidson SM, Mocanu MM, et al. The cardioprotective effect of necrostatin requires the cyclophilin-D component of the mitochondrial permeability transition pore. Cardiovasc Drugs Ther. 2007;21(6):467–469. [Epub 2007 Oct 30].
  • Zhang A, Mao X, Li L, et al. Necrostatin-1 inhibits Hmgb1-IL-23/IL-17 pathway and attenuates cardiac ischemia reperfusion injury. Transpl Int. 2014;27(10):1077–1085. [Epub 2014 May 9].
  • You Z, Savitz SI, Yang J, et al. Necrostatin-1 reduces histopathology and improves functional outcome after controlled cortical impact in mice. J Cereb Blood Flow Metab. 2008;28(9):1564–1573. [Epub 2008 May 22].
  • Northington FJ, Chavez-Valdez R, Graham EM, et al. Necrostatin decreases oxidative damage, inflammation, and injury after neonatal HI. J Cereb Blood Flow Metab. 2011;31(1):178–189. [Epub 2010 Jun 24].
  • Dong K, Zhu H, Song Z, et al. Necrostatin-1 protects photoreceptors from cell death and improves functional outcome after experimental retinal detachment. Am J Pathol. 2012;181(5):1634–1641. [Epub 2012 Sep 4].
  • Takemoto K, Hatano E, Iwaisako K, et al. Necrostatin-1 protects against reactive oxygen species (ROS)-induced hepatotoxicity in acetaminophen-induced acute liver failure. FEBS Open Bio. 2014;4:777–787. [Epub 2014 Oct 29].
  • Wang Y, Wang H, Tao Y, et al. Necroptosis inhibitor necrostatin-1 promotes cell protection and physiological function in traumatic spinal cord injury. Neuroscience. 2014;266:91–101. [Epub 2014 Feb 25].
  • Liu ZY, Wu B, Guo YS, et al. Necrostatin-1 reduces intestinal inflammation and colitis-associated tumorigenesis in mice. Am J Cancer Res. 2015;5(10):3174–3185. [Epub 2015 Dec 23].
  • Dmitriev YV, Minasian SM, Demchenko EA, et al. Study of cardioprotective effects of necroptosis inhibitors on isolated rat heart subjected to global ischemia-reperfusion. Bull Exp Biol Med. 2013;155(2):245–248. [Epub 2013 Oct 17].
  • Zheng W, Degterev A, Hsu E, et al. Structure-activity relationship study of a novel necroptosis inhibitor, necrostatin-7. Bioorg Med Chem Lett. 2008;18(18):4932–4935. [Epub 2008 Sep 5].
  • Takahashi N, Duprez L, Grootjans S, 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. [Epub 2012 Nov 30].
  • Wang D, Zhao M, Chen G, et al. The histone deacetylase inhibitor vorinostat prevents TNFα-induced necroptosis by regulating multiple signaling pathways. Apoptosis. 2013;18(11):1348–1362. [Epub 2013 May 28].
  • Cortes JE, Kantarjian H, Shah NP, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367(22):2075–2088. [Epub 2012 Nov 30].
  • O’Hare T, Shakespeare WC, Zhu X, et al. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009;16(5):401–412. [Epub 2009 Nov 3].
  • Ward JE, Stadler WM. Pazopanib in renal cell carcinoma. Clin Cancer Res. 2010;16(24):5923–5927. [Epub 2010 Nov 10].
  • van der Graaf WTA, Gelderblom H. New systemic therapy options for advanced sarcomas. Curr Treat Options Oncol. 2012;13(3):306–317. [Epub 2012 Jun 5].
  • Fauster A, Rebsamen M, Huber KV, et al. A cellular screen identifies ponatinib and pazopanib as inhibitors of necroptosis. Cell Death Dis. 2015;6:e1767. [Epub 2015 May 23].
  • Zou C, Xiong Y, Huang LY, et al. Design, synthesis, and biological evaluation of 1-Benzyl-1H-pyrazole derivatives as receptor interacting protein 1 kinase inhibitors. Chem Biol Drug Des. 2016;87(4):569–574. [Epub 2015 Nov 19].
  • Sun L, Wang H, Wang Z, et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012;148(1–2):213–227. [Epub 2012 Jan 24].
  • Harris PA, Bandyopadhyay D, Berger SB, et al. Discovery of small molecule RIP1 kinase inhibitors for the treatment of pathologies associated with necroptosis. ACS Med Chem Lett. 2013;4(12):1238–1243. [Epub 2014 Jun 6].
  • Hildebrand JM, Tanzer MC, Lucet IS, et al. Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death. Proc Natl Acad Sci USA. 2014;111(42):15072–15077. [Epub 2014 Oct 8].
  • Dodo K, Katoh M, Shimizu T, et al. Inhibition of hydrogen peroxide-induced necrotic cell death with 3-amino-2-indolylmaleimide derivatives. Bioorg Med Chem Lett. 2005;15(12):3114–3118. [Epub 2005 May 10].
  • Kim HJ, Koo SY, Ahn BH, et al. NecroX as a novel class of mitochondrial reactive oxygen species and ONOO(-) scavenger. Arch Pharm Res. 2010;33(11):1813–1823. [Epub 2010 Dec 1].
  • Orrenius S, Gogvadze V, Zhivotovsky B. Mitochondrial oxidative stress: implications for cell death. Annu Rev Pharmacol Toxicol. 2007 ;47:143–183.[Epub 2006 Oct 13].
  • Ott M, Gogvadze V, Orrenius S, et al. Mitochondria, oxidative stress and cell death. Apoptosis. 2007;12(5):913–922. [Epub 2007 Apr 25].
  • Martinet W, Schrijvers DM, De Meyer GR. Necrotic cell death in atherosclerosis. Basic Res Cardiol. 2011;106(5):749–760. [Epub 2011 May 26].
  • Choi JM, Park KM, Kim SH, et al. Effect of necrosis modulator necrox-7 on hepatic ischemia-reperfusion injury in beagle dogs. Transplant Proc. 2010;42(9):3414–3421. [Epub 2010 Nov 26].
  • Chung HK, Kim YK, Park JH, et al. The indole derivative NecroX-7 improves nonalcoholic steatohepatitis in ob/ob mice through suppression of mitochondrial ROS/RNS and inflammation. Liver Int. 2015;35(4):1341–1353. [Epub 2014 Dec 3].
  • Im KI, Kim N, Lim JY, et al. The free radical scavenger NecroX-7 attenuates acute graft-versus-host disease via reciprocal regulation of Th1/Regulatory T cells and inhibition of HMGB1 release. J Immunol. 2015;194(11):5223–5232. [Epub 2015 Apr 26].
  • Park J, Park E, Ahn BH, et al. NecroX-7 prevents oxidative stress-induced cardiomyopathy by inhibition of NADPH oxidase activity in rats. Toxicol Appl Pharmacol. 2012;263(1):1–6. [Epub 2012 Jun 5].
  • Park JH, Seo KS, Tadi S, et al. An indole derivative protects against acetaminophen-induced liver injury by directly binding to N-acetyl-p-benzoquinone imine in mice. Antioxid Redox Signal. 2013;18(14):1713–1722. [Epub 2012 Nov 6].
  • Thu VT, Kim HK, Long Le T, et al. NecroX-5 prevents hypoxia/reoxygenation injury by inhibiting the mitochondrial calcium uniporter. Cardiovasc Res. 2012;94(2):342–350. [Epub 2012 Mar 20].
  • Najjar M, Suebsuwong C, Ray SS, et al. Structure guided design of potent and selective ponatinib-based hybrid inhibitors for RIPK1. Cell Rep. 2015;10(11):1850–1860.
  • Xuan M, Okazaki M, Iwata N, et al. Chronic treatment with a water-soluble extract from the culture medium of ganoderma lucidum mycelia prevents apoptosis and necroptosis in Hypoxia/Ischemia-induced injury of type 2 diabetic mouse brain. Evid Based Complement Alternat Med. 2015;2015:865986. [Epub 2015 May/7].
  • Sanodiya BS, Thakur GS, Baghel RK, et al. Ganoderma lucidum: a potent pharmacological macrofungus. Curr Pharm Biotechnol. 2009;10(8):717–742. [Epub 2009 Nov 27].
  • Iwata N, Okazaki M, Nakano R, et al. Diabetes-mediated exacerbation of neuronal damage and inflammation after cerebral ischemia in rat: protective effects of water-soluble extract from culture medium of Ganoderma lucidum mycelia. In: Balestrino M, editor. Advances in the preclinical study of ischemic stroke. Rijeka (Croatia): Intech; 2012.
  • Lee Y, Byun HS, Seok JH, et al. Terminalia Chebula provides protection against dual modes of necroptotic and apoptotic cell death upon death receptor ligation. Sci Rep. 2016;6:25094. [Epub 2016 Apr 28].
  • Mishra V, Agrawal M, Onasanwo SA, et al. Anti-secretory and cyto-protective effects of chebulinic acid isolated from the fruits of Terminalia chebula on gastric ulcers. Phytomedicine. 2013;20(6):506–511. [Epub 2013 Mar 7].
  • Park JH, Joo HS, Yoo KY, et al. Extract from Terminalia chebula seeds protect against experimental ischemic neuronal damage via maintaining SODs and BDNF levels. Neurochem Res. 2011;36(11):2043–2050. [Epub 2011 Jun 15].
  • Silawat N, Gupta VB. Chebulic acid attenuates ischemia reperfusion induced biochemical alteration in diabetic rats. Pharm Biol. 2013;51(1):23–29. [Epub 2012 Sep 12].
  • Choi MK, Kim HG, Han JM, et al. Hepatoprotective effect of terminalia chebula against t-BHP-induced acute liver injury in C57/BL6 mice. Evid Based Complement Alternat Med. 2015;2015:517350. [Epub 2015 Feb 19].
  • Korani MS, Farbood Y, Sarkaki A, et al. Protective effects of gallic acid against chronic cerebral hypoperfusion-induced cognitive deficit and brain oxidative damage in rats. Eur J Pharmacol. 2014;733:62–67. [Epub 2014 Apr 15].
  • Walia H, Kumar S, Arora S. Comparative analysis of antioxidant and phenolic content of chloroform extract/fraction of Terminalia chebula. J Basic Clin Pharm. 2011;2(2):115–124. [Epub 2011 Mar 1].
  • Mahesh R, Bhuvana S, Begum VM. Effect of Terminalia chebula aqueous extract on oxidative stress and antioxidant status in the liver and kidney of young and aged rats. Cell Biochem Funct. 2009;27(6):358–363. [Epub 2009 Jun 24].
  • Byun HS, Park KA, Won M, et al. Phorbol 12-myristate 13-acetate protects against tumor necrosis factor (TNF)-induced necrotic cell death by modulating the recruitment of TNF receptor 1-associated death domain and receptor-interacting protein into the TNF receptor 1 signaling complex: implication for the regulatory role of protein kinase C. Mol Pharmacol. 2006;70(3):1099–1108. [Epub 2006 Jun 27].
  • Li D, Li C, Li L, et al. Natural product kongensin A is a non-canonical HSP90 inhibitor that blocks RIP3-dependent necroptosis. Cell Chem Biol. 2016;23(2):257–266. [Epub 2016 Mar 31].
  • Workman P, Burrows F, Neckers L, et al. Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Ann N Y Acad Sci. 2007;1113:202–216. [Epub 2007 May 22].
  • Trott A, West JD, Klaic L, et al. Activation of heat shock and antioxidant responses by the natural product celastrol: transcriptional signatures of a thiol-targeted molecule. Mol Biol Cell. 2008;19(3):1104–1112. [Epub 2008 Jan 18].
  • Abbas S, Bhoumik A, Dahl R, et al. Preclinical studies of celastrol and acetyl isogambogic acid in melanoma. Clin Cancer Res. 2007;13(22 Pt 1):6769–6778. [Epub 2007 Nov 17].
  • Pinna GF, Fiorucci M, Reimund JM, et al. Celastrol inhibits pro-inflammatory cytokine secretion in Crohn’s disease biopsies. Biochem Biophys Res Commun. 2004;322(3):778–786. [Epub 2004 Sep 1].
  • Shaker ME, Ashamallah SA, Houssen ME. Celastrol ameliorates murine colitis via modulating oxidative stress, inflammatory cytokines and intestinal homeostasis. Chem Biol Interact. 2014;210:26–33. [Epub 2014 Jan 5].
  • Jia Z, Xu C, Shen J, et al. The natural compound celastrol inhibits necroptosis and alleviates ulcerative colitis in mice. Int Immunopharmacol. 2015;29(2):552–559. [Epub 2015 Oct 12].
  • Chtourou Y, Fetoui H, Jemai R, et al. Naringenin reduces cholesterol-induced hepatic inflammation in rats by modulating matrix metalloproteinases-2, 9 via inhibition of nuclear factor kappaB pathway. Eur J Pharmacol. 2015;746:96–105. [Epub 2014 Dec 3].
  • Ahmed LA, Obaid AA, Zaki HF, et al. Naringenin adds to the protective effect of L-arginine in monocrotaline-induced pulmonary hypertension in rats: favorable modulation of oxidative stress, inflammation and nitric oxide. Eur J Pharm Sci. 2014;62:161–170. [Epub 2014 Jun 1].
  • Assini JM, Mulvihill EE, Sutherland BG, et al. Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr(-)/(-) mice. J Lipid Res. 2013;54(3):711–724. [Epub 2012 Dec 28].
  • Chtourou Y, Slima AB, Makni M, et al. Naringenin protects cardiac hypercholesterolemia-induced oxidative stress and subsequent necroptosis in rats. Pharmacol Rep. 2015;67(6):1090–1097. [Epub 2015 Oct 21].
  • Liu W, Fan Z, Han Y, et al. Curcumin attenuates peroxynitrite-induced neurotoxicity in spiral ganglion neurons. Neurotoxicology. 2011;32(1):150–157. [Epub 2010 Sep 28].
  • Tiwari V, Chopra K. Attenuation of oxidative stress, neuroinflammation, and apoptosis by curcumin prevents cognitive deficits in rats postnatally exposed to ethanol. Psychopharmacology (Berl). ;224(4):519–535.2012 [Epub 2012 Jul 14].
  • Luo Y, Hattori A, Munoz J, et al. Intrastriatal dopamine injection induces apoptosis through oxidation-involved activation of transcription factors AP-1 and NF-kappaB in rats. Mol Pharmacol. 1999;56(2):254–264. [Epub 1999 Jul 27].
  • Jaisin Y, Thampithak A, Meesarapee B, et al. Curcumin I protects the dopaminergic cell line SH-SY5Y from 6-hydroxydopamine-induced neurotoxicity through attenuation of p53-mediated apoptosis. Neurosci Lett. 2011 ;489(3):192–196.[Epub 2010 Dec 21].
  • Du XX, Xu HM, Jiang H, et al. Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson’s disease. Neurosci Bull. 2012;28(3):253–258. [Epub 2012 May 25].
  • Gupta SC, Prasad S, Kim JH, et al. Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep. 2011;28(12):1937–1955. [Epub 2011 Oct 8].
  • Dai MC, Zhonga ZH, Suna YH, et al. Curcumin protects against iron induced neurotoxicity in primary cortical neurons by attenuating necroptosis. Neurosci Lett. 2013;536:41–46. [Epub 2013 Jan 14].
  • Yuan J, Yuan C, Degterev A. Unsaturated heterocyclic inhibitors of necroptosis. WO 2010075290 Al. 2010.
  • Yuan J, Hsu ES. Small molecule inhibitors of necroptosis. US 20120122889 A1. 2012.
  • Yuan J, Hsu ES. Small molecule inhibitors of necroptosis. US 20140024657 A1. 2014.
  • Yuan J, Degterev A, Hitomi J, et al. Tricyclic necrostatin compounds. US 8324262 B2. 2012.
  • Yuan J, Degterev A, Cuny GD. Deuterated heterocyclic inhibitors of necroptosis. WO2014152182 A1. 2014a.
  • Yuan J, Degterev A, Cuny GD. Hybrid necroptosis inhibitors. US20140323489 A1. 2014b.
  • Cuny GD, Yuan J, Degterev A. Heterocyclic inhibitors of necroptosis. US8278344 B2. 2012.
  • Cuny GD, Teng X, Yuan J, et al. Heterocyclic inhibitors of necroptosis. US 8658689 B2. 2014a.
  • Cuny GD, Teng X, Yuan J, et al. Heterocyclic inhibitors of necroptosis.US 20140128437 A1. 2014b.
  • Cuny GD, Teng X, Yuan J, et al. Heterocyclic inhibitors of necroptosis. US 20160102053 A1. 2016.
  • Conrad M, Schick J, Proneth B, et al. Spiroquinoxaline derivatives as inhibitors of non-apoptotic regulated cell-death. WO 2015007730 A1. 2015.

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