PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 28878015-5 2017 In this study we discovered that the MLKL-modifying compound necrosulfonamide cross-links cysteine 86 of human MLKL to cysteine 32 of the thiol oxidoreductase thioredoxin-1 (Trx1). N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 61-77 mixed lineage kinase domain like pseudokinase Homo sapiens 37-41 31132314-13 2019 HepG2 cells treated with necrosulfonamide (an MLKL inhibitor) showed reduced Nile red staining and reduced SREBP1c and SCD-1 expressions. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 25-41 mixed lineage kinase domain like pseudokinase Homo sapiens 46-50 31727943-3 2019 Necrosulfonamide (NSA) binds to the 4HB domain of MLKL to inhibit necroptosis. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 0-16 mixed lineage kinase domain like pseudokinase Homo sapiens 50-54 31727943-3 2019 Necrosulfonamide (NSA) binds to the 4HB domain of MLKL to inhibit necroptosis. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 18-21 mixed lineage kinase domain like pseudokinase Homo sapiens 50-54 31727943-4 2019 To understand the molecular details of MLKL function and it"s inhibition, we have performed a molecular dynamic study on hMLKL protein in apo, phosphorylated and NSA-bound states for a total 3 mus simulation time. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 162-165 mixed lineage kinase domain like pseudokinase Homo sapiens 121-126 31727943-6 2019 NSA binding disrupts this activated form and causes two main effects on hMLKL conformation: (1) locking of the relative orientation of 4HB and PsK domains by the formation of several new interactions and (2) prevention of key 4HB residues to participate in cross-linking for oligomer formation. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 0-3 mixed lineage kinase domain like pseudokinase Homo sapiens 72-77 31727943-7 2019 This new understanding of the effect of hMLKL conformations on phosphorylation and NSA binding suggest new avenues for designing effective allosteric inhibitors of hMLKL. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 83-86 mixed lineage kinase domain like pseudokinase Homo sapiens 40-45 31129968-7 2019 Moreover, we demonstrated that this type of cell death was necroptosis and depended on RIP1-RIP3-MLKL signaling pathway because inhibition of MLKL activity by necrosulfonamide (NSA) or knockdown of RIP1 significantly attenuated cisplatin-induced cell death in HepG2/DDP-RIP3 cells. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 159-175 mixed lineage kinase domain like pseudokinase Homo sapiens 97-101 31129968-7 2019 Moreover, we demonstrated that this type of cell death was necroptosis and depended on RIP1-RIP3-MLKL signaling pathway because inhibition of MLKL activity by necrosulfonamide (NSA) or knockdown of RIP1 significantly attenuated cisplatin-induced cell death in HepG2/DDP-RIP3 cells. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 159-175 mixed lineage kinase domain like pseudokinase Homo sapiens 142-146 28923396-5 2017 Similarly, pharmacological inhibitors of RIP1 (necrostatin-1(Nec-1)), RIP3 (GSK"872) or MLKL (necrosulfonamide (NSA)) significantly reduce BV6/IFNgamma-stimulated cell death. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 94-110 mixed lineage kinase domain like pseudokinase Homo sapiens 88-92 31760070-7 2020 This latter effect was reproduced by treating primary human steatotic hepatocytes with RIPA-56 or necrosulfonamide (NSA), a specific inhibitor of human MLKL, and by knocking out (KO) MLKL in fat-loaded AML-12 mouse hepatocytes. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 98-114 mixed lineage kinase domain like pseudokinase Homo sapiens 152-156 31760070-7 2020 This latter effect was reproduced by treating primary human steatotic hepatocytes with RIPA-56 or necrosulfonamide (NSA), a specific inhibitor of human MLKL, and by knocking out (KO) MLKL in fat-loaded AML-12 mouse hepatocytes. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 116-119 mixed lineage kinase domain like pseudokinase Homo sapiens 152-156 32196619-2 2020 This research aimed to investigate the protective effect of the MLKL inhibitor necrosulfonamide (NSA) on human NP cells. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 79-95 mixed lineage kinase domain like pseudokinase Homo sapiens 64-68 32075957-8 2020 Further, we discovered that both the inhibitor of RIPK1 R-7-Cl-O-Necrostatin-1 (Nec-1s) and MLKL-inhibitor necrosulfonamide (NSA) suppressed necroptosis in HaCaT cells and IMQ mouse models, powerfully blocked IMQ-induced inflammatory responses in vivo, and significantly downregulated the production of inflammatory factors like IL-1beta, IL-6, IL-17A, IL-23a, CXCL1, and CCL20. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 107-123 mixed lineage kinase domain like pseudokinase Homo sapiens 92-96 32075957-8 2020 Further, we discovered that both the inhibitor of RIPK1 R-7-Cl-O-Necrostatin-1 (Nec-1s) and MLKL-inhibitor necrosulfonamide (NSA) suppressed necroptosis in HaCaT cells and IMQ mouse models, powerfully blocked IMQ-induced inflammatory responses in vivo, and significantly downregulated the production of inflammatory factors like IL-1beta, IL-6, IL-17A, IL-23a, CXCL1, and CCL20. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 125-128 mixed lineage kinase domain like pseudokinase Homo sapiens 92-96 31894265-6 2020 The antitumor effects of OPD" were also inhibited by a mixed lineage kinase domain-like protein (MLKL) inhibitor necrosulfonamide. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 113-129 mixed lineage kinase domain like pseudokinase Homo sapiens 55-95 31894265-6 2020 The antitumor effects of OPD" were also inhibited by a mixed lineage kinase domain-like protein (MLKL) inhibitor necrosulfonamide. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 113-129 mixed lineage kinase domain like pseudokinase Homo sapiens 97-101 29101355-4 2017 In human neutrophils receptor-interacting protein kinase (RIPK)-1 inhibition with necrostatin-1s or mixed lineage kinase domain-like (MLKL) inhibition with necrosulfonamide abrogated cell death and associated-neutrophil extracellular DNA release induced by all of the aforementioned particles. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 156-172 mixed lineage kinase domain like pseudokinase Homo sapiens 100-132 29101355-4 2017 In human neutrophils receptor-interacting protein kinase (RIPK)-1 inhibition with necrostatin-1s or mixed lineage kinase domain-like (MLKL) inhibition with necrosulfonamide abrogated cell death and associated-neutrophil extracellular DNA release induced by all of the aforementioned particles. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 156-172 mixed lineage kinase domain like pseudokinase Homo sapiens 134-138 28878015-5 2017 In this study we discovered that the MLKL-modifying compound necrosulfonamide cross-links cysteine 86 of human MLKL to cysteine 32 of the thiol oxidoreductase thioredoxin-1 (Trx1). N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 61-77 mixed lineage kinase domain like pseudokinase Homo sapiens 111-115 26817517-7 2016 Furthermore, necrostatin-1 and necrosulfonamide, an inhibitor for human MLKL suppress crystal-induced cell death in human renal progenitor cells. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 31-47 mixed lineage kinase domain like pseudokinase Homo sapiens 72-76 28088644-8 2017 RIP1 inhibitor necrostatin-1 (Nec-1), MLKL inhibitor necrosulfonamide (NSA) and silencing RIP1, RIP3, and MLKL inhibited t-BHPH-induced cell death while pan-caspase inhibitor Z-VAD-FMK showed no effect. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 53-69 mixed lineage kinase domain like pseudokinase Homo sapiens 38-42 27756752-5 2016 Furthermore, blocking RIP1/RIP3/MLKL-dependent signaling using chemical inhibitors necrostatin-1 (Nec-1) and necrosulfonamide (NSA) synergizes with BSO and auranofin in killing TSC-deficient cells. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 109-125 mixed lineage kinase domain like pseudokinase Homo sapiens 32-36 28827318-9 2017 Finally, the compound necrosulfonamide conjugates cysteine 86 of human MLKL and blocks MLKL polymer formation and subsequent cell death. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 22-38 mixed lineage kinase domain like pseudokinase Homo sapiens 71-75 28827318-9 2017 Finally, the compound necrosulfonamide conjugates cysteine 86 of human MLKL and blocks MLKL polymer formation and subsequent cell death. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 22-38 mixed lineage kinase domain like pseudokinase Homo sapiens 87-91 26028172-8 2015 Of note, the Receptor-Interacting Protein (RIP)1 inhibitor necrostatin-1 (Nec-1) or the Mixed Lineage Kinase Domain-Like protein (MLKL) inhibitor necrosulfonamide (NSA) significantly reduce BV6/MS275-induced cell death in the presence of zVAD.fmk, suggesting that BV6/MS275 cotreatment triggers necroptosis when caspases are inhibited. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 146-162 mixed lineage kinase domain like pseudokinase Homo sapiens 88-128 26531064-3 2016 Here, we show that the receptor-interacting protein kinase (RIPK)-1-stabilizers necrostatin-1 or necrostatin-1s and the mixed lineage kinase domain-like (MLKL)-inhibitor necrosulfonamide prevent monosodium urate (MSU) crystal- or PMA-induced NET formation in human and mouse neutrophils. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 170-186 mixed lineage kinase domain like pseudokinase Homo sapiens 120-152 26531064-3 2016 Here, we show that the receptor-interacting protein kinase (RIPK)-1-stabilizers necrostatin-1 or necrostatin-1s and the mixed lineage kinase domain-like (MLKL)-inhibitor necrosulfonamide prevent monosodium urate (MSU) crystal- or PMA-induced NET formation in human and mouse neutrophils. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 170-186 mixed lineage kinase domain like pseudokinase Homo sapiens 154-158 26028172-8 2015 Of note, the Receptor-Interacting Protein (RIP)1 inhibitor necrostatin-1 (Nec-1) or the Mixed Lineage Kinase Domain-Like protein (MLKL) inhibitor necrosulfonamide (NSA) significantly reduce BV6/MS275-induced cell death in the presence of zVAD.fmk, suggesting that BV6/MS275 cotreatment triggers necroptosis when caspases are inhibited. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 146-162 mixed lineage kinase domain like pseudokinase Homo sapiens 130-134 25593994-7 2014 Inhibition of the RIPK3 substrate MLKL with necrosulfonamide also increased apoptosis in edelfosine-treated cells. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 44-60 mixed lineage kinase domain like pseudokinase Homo sapiens 34-38 32297735-9 2020 For instance, in the development of downstream programmed necrosis (or necroptosis) inhibitor necrosulfonamide, we used a chemical probe to unveil a functional protein that was not previously implicated in necroptosis, mixed lineage kinase domain-like protein (MLKL). N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 94-110 mixed lineage kinase domain like pseudokinase Homo sapiens 219-259 32297735-9 2020 For instance, in the development of downstream programmed necrosis (or necroptosis) inhibitor necrosulfonamide, we used a chemical probe to unveil a functional protein that was not previously implicated in necroptosis, mixed lineage kinase domain-like protein (MLKL). N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 94-110 mixed lineage kinase domain like pseudokinase Homo sapiens 261-265 25766324-11 2015 The RIPK1 inhibitor necrostatin-1 and the MLKL-blocker necrosulfonamide significantly reduced this form of cell death. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 55-71 mixed lineage kinase domain like pseudokinase Homo sapiens 42-46 22265413-4 2012 An affinity probe derived from necrosulfonamide and coimmunoprecipitation using anti-RIP3 antibodies both identified the mixed lineage kinase domain-like protein (MLKL) as the interacting target. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 31-47 mixed lineage kinase domain like pseudokinase Homo sapiens 121-161 22265413-4 2012 An affinity probe derived from necrosulfonamide and coimmunoprecipitation using anti-RIP3 antibodies both identified the mixed lineage kinase domain-like protein (MLKL) as the interacting target. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 31-47 mixed lineage kinase domain like pseudokinase Homo sapiens 163-167 22860037-8 2012 Moreover both the staurosporine-triggered and the classical death ligand-induced necroptotic pathway can be effectively arrested by a lysosomal enzyme inhibitor CA-074-OMe and the recently discovered MLKL inhibitor necrosulfonamide. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 215-231 mixed lineage kinase domain like pseudokinase Homo sapiens 200-204 33318170-7 2020 Finally, we show that the other well-known MLKL inhibitor Necrosulfonamide, which also covalently modifies Cys86, must employ a different mode of action. N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 58-74 mixed lineage kinase domain like pseudokinase Homo sapiens 43-47