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5-(1H-indol-3-ylmethyl)-3-methyl-2-sulfanylidene-4-imidazolidinone inhibits RIPK1. 124 / 124
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"Inhibition of RIP1 by Necrostatin-1 partially rescued cells from imatinib deprivation induced cell death, indicating that this necrotic and necroptotic signaling pathway substitutes for the blocked apoptosis at least partially."
21949869
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"In contrast, RIP1 expression in mouse liver remained unchanged following ethanol feeding and inhibition of RIP1 kinase by necrostatin-1 did not attenuate ethanol-induced hepatocyte injury."
23319235
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"We also included necrostatin-1, which inhibits RIP1 kinase activity and therefore necroptosis."
27302486
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"The LPS or bacterial induced necroptosis in wild type BMDMs was also inhibited by Necrostatin-1 (Nec-1), indicating a RIPK1 kinase dependency (XREF_SUPPLEMENTARY)."
27264187
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"Necroptosis is a caspase independent cell death and necrostatin-1 inhibits the activity of RIP1 and blocks the necroptosis pathway."
| PMC
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"Inhibition of RIP1 by necrostatin-1 clearly protected from TNF induced necroptosis in all three L929 sublines, but had no effect on the course of MNNG induced necrosis over 16h."
23760205
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"Additionally, while the effect of Y100 was abrogated by necrostatin-1 (an inhibitor of the necroptosis effector RIPK1), neither siRNA mediated knockdown of RIPK1 nor inhibition of RIPK3 with GSK ' 872 was sufficient to prevent Y100 mediated cell death (XREF_SUPPLEMENTARY and XREF_SUPPLEMENTARY)."
29662612
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"It can be inhibited either with Necrostatin-1 (Nec-1), by blocking the activity of the RIPK1 receptor, or with GSK872 which inhibits RIPK3 [261,262]."
| PMC
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"The apoptosis component is RIPK1 dependent, which is sensitive to RIPK1 kinase inactivation by necrostatin-1."
35597275
sparser
"Inhibition of RIP1 by necrostatin-1 did not inhibit A1-IRS activity, thereby excluding necroptosis ( xref ). xref We also looked for mitochondrial perturbation and did not observe any cytochrome C redistribution ( xref ) or ROS increase ( xref ) after incubation with A1-IRS, and mitochondria appeared normal when observed under electronic microscopy (data not shown)."
25356869
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"A key inhibitor of RIPK1 kinase in the necroptosis pathway, necrostatin-1 (Nec-1), inhibits RIPK1/RIPK3/MLKL signaling, and thus might inhibit alcohol-induced osteopenia through decreased activation of osteoblast necroptosis (28)."
36339402
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"Inhibition of RIP-1 by Necrostatin-1 also did not alter cell death in male or female cells (not shown)."
23928697
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"Indeed, inhibition of RIP1 by necrostatin-1 abolishes both apoptosis and necrosis in RPE cells."
28615451
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"Generally, necroptosis is defined as cell death mediated through a pathway that depends on the RIPK1-RIPK3 complex that may be inhibited by necrostatin-1 (Nec-1) ( xref )."
27177159
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"In an OS model, RIPK1 mediated necroptosis was confirmed as the main cell death mechanism involved in Shikonin therapy, as only Necrostatin-1 (an inhibitor of RIPK1) was able to induce treatment reversion."
25905041
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"Inhibition of RIP-1 by Necrostatin-1 also did not alter cell death in male or female cells (not shown)."
23928697
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"Inhibition of RIPK1 by Necrostatin-1s (Nec1s) resulted in reduced, but not totally inhibited, caspase activation and cell death, demonstrating simultaneous occurrence of RIPK1 kinase-dependent and -independent apoptosis (Fig. xref )."
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"64 Indeed, genetic deletion of RIPK3 in Casp8 -/- dendritic cells rescues LPS induced IL-1beta production from Casp8 -/- dendritic cells, and necrostatin-1 (a chemical inhibitor of RIPK1 kinase activi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25451151
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"Necrostatin-1 pretreatment markedly reduced IR-induced muscle damage and RIPK1, Bok, and cleaved caspase-3 expression, whereas upregualted Bcl-2 expression (p < 0.05)."
36599139
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"Necroptosis induction requires the activity of RIP-1 kinase, which can be repressed by necrostatin-1 (Nec-1)."
25725104
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"In contrast, necroptosis inhibitors necrosulfonamide (NSA) and necrostatin-1s (Nec-1s) which inhibits MLKL and RIPK1 respectively, partially (to 68–72% of control cell viability) prevented FAC and erastin-induced cell death in the IB3-1 CF cells (Fig.  xref A)."
34903297
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"Indeed, inhibition of RIP1 by necrostatin-1 abolishes both apoptosis and necrosis in RPE cells."
28615451
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"Inhibition of RIP1 by necrostatin-1 clearly protected from TNF-induced necroptosis in all three L929 sublines, but had no effect on the course of MNNG-induced necrosis over 16 h (Fig.  xref b)."
23760205
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"These results show that degradation of cIAP1/2 by LCL161 and inactivation of RIPK1 by necrostatin-1 results in death of normal macrophages and suggest that cIAP1/2 and RIPK1 play an important role in regulating viability of human macrophages."
34824340
tas
No evidence text available
27992216
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"RIPK1 inhibition by necrostatin-1 (10) and MLKL inhibition by necrosulfonamide protects against ischemic brain injury (8,11)."
30394012
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"Functional analysis showed that the inhibition of RIP1 caused by necrostatin-1 (Nec-1) inhibited the proliferation, simultaneously facilitate both the apoptosis and differentiation of AML cells."
35370472
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"Though Necrostatin-1 has been widely used to inhibit RIPK1 kinase activity, off-target effects have been reported."
28366204
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"The pharmacologic small molecule necrostatin 1 inhibits RIPK1 and prevents necroptosis in most cellular models -- a very useful experimental tool."
23720337
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"26 Here, we show that LTX-315 also can induce ICD in the context of a necrotic pathway that is independent of RIP3 (and is not inhibited by necrostatin 1, which inhibits RIP1), XREF_BIBR, XREF_BIBR suggesting that different pathways leading to necrosis can cause ICD."
26962684
tas
No evidence text available
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"Necrostatin-1 specifically inhibits RIP1 kinase and disrupts regulated necrosis in tissue culture XREF_BIBR - XREF_BIBR."
23145018
sparser
"In the other hand, the inhibition of RIPK1 by necrostatin-1 is still controversial: protective xref and deleterious xref , xref roles have been reported."
32221312
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"Z-VAD-FMK (a caspase inhibitor) and necrostatin-1 (a specific inhibitor of RIPK1) were utilized to determine whether the cell death was mediated by RIPK1 or caspases."
29760660
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"Necrostatin-1 blocks necroptosis in many settings by interacting and inhibiting RIPK1 kinase activity, which is required for activation of RIPK3."
26491219
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"For this, we used necrostatin-1 (Nec1) to inhibit RIPK1, necrosulfonamide (NSA) to inhibit MLKL and siRNA to silence RIPK3."
33378358
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"And, necrostatin-1 could effectively reverse the changes of pulmonary fibrosis, RIPK1, RIPK3, and ECM in vivo and in vitro experiments."
32019905
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"In vitro, human neutrophils fed CA-MRSA lyse by an unknown mechanism that is inhibited by necrostatin-1, an allosteric inhibitor of receptor interacting serine/threonine kinase 1 (RIPK-1)."
28473408
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"Inhibiting RIPK1 and RIPK3 by their inhibitors Necrostatin-1 (Nec-1) and GSK-872, respectively, showed effective activities against osteoclast differentiation and bone resorption induced by receptor activator of nuclear factor-κB ligand (Rankl)."
32321638
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"The addition of necrostatin-1 inhibited the cell death induced by T+S+V in both the mock and VZV infected populations, confirming the involvement of RIPK1 in this cell death pathway."
32649716
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"Rotenone induced mitochondrial ROS activate necroptosis via RIP1, which is totally abolished by necrostatin-1."
33672490
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"S. aureus can also trigger necroptosis, cell death dependent on RIPK1, RIPK3, and MLKL that can be blocked by necrostatin-1 and necrosulfonamide (NSA)."
27460814
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"We found that RIP-1 expression was upregulated in the lung of ALI mice and inhibition of RIP-1 by necrostatin-1 significantly prolonged the survival time of mice, which was accompanied by less serve lung injury."
29199874
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"These suggested that necrostatin-1 limited the upregulation of RIP1 and NF-κB induced by chronic stress in D-galactose-induced aging mice."
30356849
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"However, it is certain that Ser161 contributes to necrostatin-1 (Nec-1)-mediated inhibition of RIP1 kinase activity."
27383048
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"DAPE induced reduction of NCI-H28 cell viability was partially inhibited by necrostatin-1, an inhibitor of RIP1 kinase to induce necroptosis, or knocking-down RIP1."
26004138
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"Importantly, treatment with necrostatin-1 (nec-1) (78) ( Figure S4 ) or GSK-872 (79) ( Figure 5F ), inhibitors of RIPK1 and RIPK3, respectively, reversed the effects of FAK inhibition and restored cell viability to levels comparable to control macrophages."
34745115
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"Necrostatin-1 specifically inhibits the pro necrotic RIP1 kinase activity, but not the kinase activities of other kinases including RIP2 and RIP3 [XREF_BIBR, XREF_BIBR]."
20532807
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"The role of necroptosis in cardiac I/R injury was first demonstrated using the small molecule inhibitor necrostatin-1 and its optimized analog necrostatin-1 s, which allosterically inhibit RIPK1 kinase activity [54,109]."
35597275
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"Necrostatin-1 treatment abrogated association of RIPK1 and MLKL with ATG5 (XREF_FIG), indicating a requirement for RIPK1 kinase activity for complex formation."
27219062
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"In addition, it was identified that the increased RIPK1 and RIPK3 can be inhibited by necrostatin-1 in both in vivo and in vitro."
32345086
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"Inhibition of RIP1 by Necrostatin-1 and even more effectively p38-MAPK inhibition by the p38 inhibitor III rescued cells from imatinib deprivation induced cell death (XREF_FIG, right panel), indicating that these proteins play a major role for cell death upon oncogenic stress."
21949869
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"Moreover, RIP1 inhibition by necrostatin-1 only reduces mitochondrial but not cytosolic ROS elevation."
26381601
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"RIPK1 inhibition by necrostatin-1 ( xref ) and MLKL inhibition by necrosulfonamide protect against ischemic brain injury ( xref , xref )."
30394012
sparser
"Inhibiting RIPK1 by necrostatin-1 strikingly mitigated cognitive impairment and alleviated postoperative amplified neuroinflammation, necroptosis and GluA1 loss in hippocampus."
30042663
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"Necroptosis is another pathway leading to programmed cell death; necroptosis is inhibited by necrostatin-1 which blocks RIP1 kinase, an essential component of the pathway [XREF_BIBR, XREF_BIBR]."
28622381
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"Another study showed that targeting necroptosis signalling with the specific RIPK1 antagonist Necrostatin-1 or genetic deletion of Mlkl systemically in vivo, partially protected mice from inferior vena cava ligation induced venous thrombosis 62."
33510145
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No evidence text available
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"Further, Necrostatin-1 (Nec-1) -- an inhibitor of RIP1 kinase activity -- dramatically increased baculoviral transgene expression in RIP1 silenced cells."
28831401
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"Timing dependent, necrostatin-1 diminished RIPK1 (P < 0.001), and aborted the necroptosis induced renal cell injury."
35090059
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"The necrostatin-1 inhibits RIP1 kinase activity, which is required to trigger necroptosis pathway."
28947974
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"Moreover, necrostatin-1, an inhibitor that targets RIP-1, has been shown to exert neuroprotective functions and to shield neurons from cell death following CCI-TBI."
22437344
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"Furthermore, heme mediated cell death is unaffected by the addition of necrostatin-1 (a specific inhibitor of RIP1) (results not shown)."
26270345
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"Necrostatin-1 (an inhibitor of RIPK1, RIPK3-KO, and MLKL-KO) mice were recently used to demonstrate the role of necroptosis in IR- and cisplatin induced AKI."
26924060
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"The RIP1 antagonist necrostatin-1 prevented the loss of ES-MNs exposed to either mutSOD1 or sALS (XREF_FIG) astrocytes."
24508385
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"Necrostatin-1 inhibits RIPK1 by blocking its association with RIP3."
29212215
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"Necrostatin-1 blocks both RIPK1 and IDO : consequences for the study of cell death in experimental disease models."
23197293
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"RIPK1 inhibition by necrostatin-1 (10) and MLKL inhibition by necrosulfonamide protect against ischemic brain injury (8,11)."
30394012
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"Inhibition of RIP1 by necrostatin-1 did not inhibit A1-IRS activity, thereby excluding necroptosis (XREF_SUPPLEMENTARY)."
25356869
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"Necrostatin-1 inhibits the kinase activity of RIP1 26 while necrosulfonamide targets MLKL, which has recently emerged as a key signaling protein that mediates binding to downstream targets."
23985697
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"Necrostatin-1 specifically inhibits RIP1 kinase and disrupts regulated necrosis in tissue culture xref – xref ."
23145018
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"ZVAD-FMK (an inhibitor of pan-caspase), necrostatin-1 (a selective inhibitor of RIPK1), and chloroquine (an inhibitor of autophagy by raising the lysosomal pH) can not block ferroptosis [XREF_BIBR]."
29038744
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"Recently, receptor interacting protein-1 (RIP1)-dependent necrosis, which is inhibited by necrostatin-1, an inhibitor of RIP1, has emerged as a form of regulated necrosis."
21888904
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"XREF_BIBR and XREF_BIBR Although inhibition of necroptosis by RIP3 deficiency, RIP1 blockade by necrostatin-1, or MLKL deficiency all reduce cell death at early time points, XREF_BIBR and XREF_BIBR RIP3 deficiency was unable to abrogate acetaminophen induced liver injury at 24 hours."
25046161
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"In addition, necroptosis can be manipulated by inhibitors such as Necrostatin 1, which blocks RIP1 kinase activity."
26500646
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"Furthermore, we tested an inactive analog of necrostatin-1, necrostatin-1I, which does not inhibit RIPK1 or necroptosis in other settings."
23386613
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"Necrostatin-1 administration inhibited the upregulation of RIP1 and RIP3 and enhanced the expression of caspase-8 in DSS induced colitis."
26693068
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"9 Generation of the kinase receptor interacting protein 1 (RIP1)/RIP3 containing ' necrosomes ' activates downstream necroptotic signaling, which can be inhibited by necrostatin 1 (XREF_FIG)."
24336086
sparser
"Here, we investigated whether inhibiting RIPK1 by necrostatin-1 (Nec-1) could limit neuroinflammation and attenuate POCD in D-Galactose (D-Gal)-induced aged mice."
30042663
sparser
"Necrostatin-1 (Nec-1) inhibits receptor-interacting protein 1 (RIP1) kinase and programmed necrosis."
24198446
sparser
"We found that RIP-1 expression was upregulated in the lung of ALI mice and inhibition of RIP-1 by necrostatin-1 significantly prolonged the survival time of mice, which was accompanied by less serve lung injury."
29199874
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"6 Necrostatin-1 (Nec-1) prevents necroptosis by binding to and inactivating RIP1."
28250973
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"Since necrostatin-1 has been shown to block not only RIPK1 but also indoleamine 2,3-dioxygenase (IDO), the IDO2 specific inhibitor 1-methyl-D-tryptophan (1-MT) was added to BMDC cultures as a control."
24808358
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"In line with its essential role in programmed necrosis, pharmacological inhibition of RIPK1 by necrostatin-1 protected the same subset of sensitive tumor cell lines that we had used for analysis in Figure XREF_FIG d (resistant KNS-62 cells were again included as control) from both TRAIL/zVAD/CHX- and TNF/zVAD/CHX induced programmed necrosis."
24507727
sparser
"Necroptosis was significantly reduced when RIP1 kinase was inhibited by necrostatin-1, whereas inhibition of caspases with z-vad-fmk, an irreversible pan-caspase inhibitor, did not prevent necroptosis."
22372834
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"Necrostatin-1 inhibits receptor-interacting serine/threonine-protein kinase 1 (RIPK1) to initiate necroptosis; it also inhibits indoleamine 2,3-dioxygenase (IDO) to regulate tumor immunity."
34572979
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"We further explored whether necrostatin-1 treatment could inhibit RIPK1 kinase and investigated its effects on the downstream signaling pathway of RIPK1 with EtOH intervention."
34745415
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"Necrostatin-1 inhibited RIP1 dependent necrosis in murine hearts, leading to infarct size reduction and preservation of cardiac function in magnetic resonance imaging (MRI) scans 28 days after I/R injury [XREF_BIBR]."
| PMC
sparser
"Moreover, RIP1 inhibition by necrostatin-1 only reduces mitochondrial but not cytosolic ROS elevation (Fig.  xref )."
26381601
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"Necrostatin-1 (Nec-1) specifically blocks the kinase activity of RIPK1 [XREF_BIBR]."
23301705
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"This is consistent with the notion that Necrostatin-1 inhibits RIPK1 kinase activity, which is required for the formation of RIPK1/FADD/caspase -8 complex (Degterev et al., 2008; Wang et al., 2008)."
19524512
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"This TNF-alpha and Fas-induced cell death is a type of receptor interacting protein-1 (RIP-1)-dependent programmed necrosis called necroptosis, which can be prevented by necrostatin-1, a specific RIP-1 inhibitor."
21989986
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"Inhibition of RIP1 by Necrostatin-1 partially rescued cells from imatinib deprivation-induced cell death, indicating that this necrotic/necroptotic signaling pathway substitutes for the blocked apoptosis at least partially."
21949869
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"20 Necrostatin-1 and an optimized derivative of necrostatin-1 (7-Cl-O-Nec-1) are small molecules inhibitors of RIP1."
25563840
sparser
"While the expression of RIP1 in mouse liver tissues had no change following ethanol feeding, and inhibition of RIP1 kinase by necrostatin-1 did not mitigate ethanol-induced hepatocyte injury [ xref ]."
33374660
sparser
"Inhibition of RIP1 by Necrostatin-1 and even more effectively p38-MAPK inhibition by the p38 inhibitor III rescued cells from imatinib deprivation induced cell death ( xref , right panel), indicating that these proteins play a major role for cell death upon oncogenic stress."
21949869
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"In the second approach, we turned to a fragment based strategy, combining a hinge binding fragment of ponatinib with a highly selective necrostatin-1 inhibitor of RIPK1."
26472031
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"Inhibition of RIP-1 by Necrostatin-1 (Nec-1) in SW620 cells ameliorated cell death and AIF translocation after AA005 treatment (Figure  xref B, C), whereas AIF knockdown failed to affect the increase in RIP-1 evoked by AA005 (Figure  xref D)."
25885900
sparser
"The first stage of the work was to study the effect of RIPK1 inhibition by necrostatin-1 under physiological conditions."
35054920
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"To determine if necroptosis was involved in the neurotoxicity induced by miR-21, we treated the cultures with necrostatin-1, which specifically inhibits RIPK-1."
26154133
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"Inhibition of RIP-1 by Necrostatin-1 (Nec-1) in SW620 cells ameliorated cell death and AIF translocation after AA005 treatment, whereas AIF knockdown failed to affect the increase in RIP-1 evoked by AA005."
25885900
sparser
"Thus, we here induced aged mice via intraperitoneal injection of D-Gal for 2 months and detected the effects of inhibiting RIPK1 by necrostatin-1 (Nec-1; Yang et al., xref ) on POCD in the aged mice."
30042663
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"In particular, necrostatin-1 has been identified to specifically inhibit the kinase activity of RIP1, thereby undermining its interaction with RIP3 and antagonizing necroptosis, without affecting NF-kappaB XREF_BIBR."
24714696
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"In a previous study, we showed that expression of the tnt gene in Jurkat T cells (Jurkat 655-TNT) induced a necrotic like cell death that was not prevented by necrostatin-1, indicating RIPK1 independent necrosis."
29996103
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"Furthermore, necrostatin-1 significantly downregulated necroptosis related proteins (MLKL, RIP1, and RIP3) and apoptosis related proteins (cleaved-Caspase-3, Bax), and it upregulated the expression of anti-apoptotic protein Bcl-2."
31719260
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"A necrostatin-1 dose response for the concentration of necrostatin-1 required to inhibit the RIP1 activity in U1 cells was determined by EGFRvIII driven phosphorylation of phospho-p65 (XREF_SUPPLEMENTARY)."
23972990
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"Necroptosis was significantly reduced when RIP1 kinase was inhibited by necrostatin-1, whereas inhibition of caspases with z-vad-fmk, an irreversible pan-caspase inhibitor, did not prevent necroptosis."
22372834
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"Inhibition of necroptosis effectors RIPK1 by the small molecule inhibitor Necrostatin-1 was sufficient to rescue multiple CRC cell lines from ddC, AZA, and combination ddC+AZA mediated toxicity ( xref )."
35320348
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"Addition of necrostatin-1 to block RIPK1 kinase also partially inhibited cell death induced by the two IKK inhibitors (Fig. 4a) with a modest effect on Caspase-8, Caspase-3, and PARP cleavage (Fig. 4b)."
32024820
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"Conversely, necroptosis is dependent on RIP1 kinase activity, which can by inhibited by necrostatin-1 (nec-1)."
23555634
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"Necrostatin-1 (Nec-1) inhibits receptor interacting protein 1 (RIP1) kinase and programmed necrosis."
24198446
sparser
"RIPK1 inhibition by necrostatin-1 ( xref ) and MLKL inhibition by necrosulfonamide protects against ischemic brain injury ( xref , xref )."
30394012
sparser
"In line with its essential role in programmed necrosis, pharmacological inhibition of RIPK1 by necrostatin-1 protected the same subset of sensitive tumor cell lines that we had used for analysis in Figure  xref d (resistant KNS-62 cells were again included as control) from both TRAIL/zVAD/CHX- and TNF/zVAD/CHX-induced programmed necrosis (Figure  xref a)."
24507727
reach
"By using a chemical approach, we showed that pretreatment of mice with Necrostatin-1 (Nec-1) (inhibitor of RIPK1) and/or PJ34 (inhibitor of PARP-1) significantly protected mice against concanavalin A (ConA) liver injury (aspartate amino-transferase (AST)/alanine amino-transferase (ALT)) associated with down-regulated hepatocyte specific IL-33 expression."
25747661
sparser
"However, inhibiting Ripk1 directly by necrostatin-1 did not rescue cell death induced by N-Gsdma3, indicating that mitochondrial targeting is crucial for Gsdma3 activation."
26100518
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"Conversely, inhibition of RIPK1 by necrostatin-1 marginally reduced LDH release from RSV infected macrophages (data not shown)."
32854254
sparser
"The apoptosis component is RIPK1 dependent, which is sensitive to RIPK1 kinase inactivation by necrostatin-1."
35597275
sparser
"In addition, it was identified that the increased RIPK1 and RIPK3 can be inhibited by necrostatin-1 in both in vivo and in vitro ."
32345086
reach
"It was used different inhibitors of cell death : Z-VAD, a pan-caspase inhibitor that blocks apoptosis; Necrostatin-1, which inhibits RIPK1 activity and blocks necroptosis; and the iron chelator, deferoxamine, that chelates iron and prevents ferroptosis."
32932214
sparser
"However, it should be noted that, although inhibition of RIP1 kinase by necrostatin-1 did not have an effect on the cytotoxic activity of NaD1, the ability of NaD1 to effect the necroptotic pathway downstream of RIP1 kinase activity, such as via direct modulation of MLKL-mediated membrane disruption, xref not addressed in our current study should be determined to eliminate definitively necroptosis as having a role."
28179997
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"Mechanistically, we show that inactivation of RIP1 by necrostatin-1 suppressed nuclear factor kappaB (NF-kappaB) cascade signals, including activation of IKKalpha, nuclear factor kappa B inhibitor protein alpha (IkappaBalpha), accumulation of nuclear p65 and NF-kappaB promoter activity."
30372886
signor
"The interaction between rip1 and rip3 is abolished by the rip1 kinase inhibitor necrostatin-1."
19524513
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"In rodents, it has previously been shown that necrostatin-1 (Nec-1) inhibits RIP1, a central regulator of programmed necrosis, thereby decreasing cell death and reducing infarct size (IS) after ischaemia and reperfusion (I/R) injury."
25496079
reach
"Necrostatin-1 blocks the association of RIP1 with RIP3, leading to RIP3 instability, and cleavage from a 57-kDa to a 55-kDa protein."
29212215