This panel provides drug-protein interaction and their ADRs along with references
| Toxicity |
Interacting Protein |
Mechanism |
Reference |
| Apoptosis | Myb proto-oncogene protein (P10242) | Differential apoptosis by indomethacin in gastric epithelial cells through the constitutive expression of wild-type p53 and/or up-regulation of c-myc [ ADR Type 2 ] | Differential apoptosis by indomethacin in gastric epithelial cells through the constitutive expression of wild-type p53 and/or up-regulation of c-myc
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| Apoptosis | wild-type p53 (P04637) | Differential apoptosis by indomethacin in gastric epithelial cells through the constitutive expression of wild-type p53 and/or up-regulation of c-myc [ ADR Type 2 ] | Differential apoptosis by indomethacin in gastric epithelial cells through the constitutive expression of wild-type p53 and/or up-regulation of c-myc
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| Arrests Endothelial Cell Proliferation | BCL oncogene (P24385) | Indomethacin significantly inhibited basal and bFGF-stimulated endothelial cell proliferation@which is correlated significantly with reduced cyclin D1 and increased p21 protein expression@suggestting that indomethacin arrests endothelial cell proliferation essential for angiogenesis by modulating cell cycle protein levels [ ADR Type 2 ] | Indomethacin inhibits endothelial cell proliferation by suppressing cell cycle proteins and PRB phosphorylation: a key to its antiangiogenic action?
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| Arrests Endothelial Cell Proliferation | P21 protein (P78460) | Indomethacin significantly inhibited basal and bFGF-stimulated endothelial cell proliferation@which is correlated significantly with reduced cyclin D1 and increased p21 protein expression@suggestting that indomethacin arrests endothelial cell proliferation essential for angiogenesis by modulating cell cycle protein levels. [ ADR Type 2 ] | Indomethacin inhibits endothelial cell proliferation by suppressing cell cycle proteins and PRB phosphorylation: a key to its antiangiogenic action?
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| Cytotoxicity | Multidrug resistance-associated protein (P33527) | Indomethacin inhibites the activity of MDR-associated protein (MRP)@ thus increases the Cytotoxicity of doxorubicin [ ADR Type 4 ] | P-glycoprotein and multidrug resistance-associated protein mediate specific patterns of multidrug resistance in malignant glioma cell lines, but not in primary glioma cells
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| Denatured Proteins | Heat shock 70 kDa protein (O43301) | In these cells,the 70-kDa constitutive heat shock protein exhibited an enhanced aggregation in the presence of indomethacin,suggestting that indomethacin at moderate temperatures accelerates the presence of denatured proteins in the cell, thus lowering the temperature threshold for a heat shock response [ ADR Type 1 ] | Enhanced protein denaturation in indomethacin-treated cells Cell Stress
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| Enhance Contractility Of The Small Intestine | Acetylcholinesterase precursor (P22303) | Treatment of the rat with indomethacin decreased responsiveness of enteric neurons with the progression of lesions owing to diminution of acetylcholinesterase activity [ ADR Type 3 ] | Indomethacin-induced lesion modifies contractile activity in rat small intestines Scand
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| Enterocolitis | B2 bradykinin receptor (P30411) | B2 receptors were identified in both normal and inflammatory intestine with more prominent specific immunohistochemical staining in the acutely inflamed tissue@@which play a role in indomethacin induced enterocolitis in genetically susceptible Lewis rats [ ADR Type 5 ] | Kallikrein-kininogen system activation and bradykinin (B2) receptors in indomethacin induced enterocolitis in genetically susceptible Lewis rats
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| Enterocolitis | High molecular weight kininogen II (Q6DMP4) | Rats displayed K-K system activation manifested by a significant decrease in plasma prekallikrein and HK functional levels@which play a role in indomethacin induced enterocolitis in genetically susceptible Lewis rats. [ ADR Type 3 ] | Kallikrein-kininogen system activation and bradykinin (B2) receptors in indomethacin induced enterocolitis in genetically susceptible Lewis rats
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| Enterocolitis | Plasma kallikrein (P03952) | Rats displayed K-K system activation manifested by a significant decrease in plasma prekallikrein and HK functional levels,which play a role in indomethacin induced enterocolitis in genetically susceptible Lewis rats [ ADR Type 3 ] | Kallikrein-kininogen system activation and bradykinin (B2) receptors in indomethacin induced enterocolitis in genetically susceptible Lewis rats
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| Experimental Dystonia | Integrin alpha-M (P11215) | Induce barrel rotation in the rat;experimental dystonia.Despite a reduction in ICAM-1 after 24 h@ ICAM-1@ in concert with Mac-1@ contributes to mucosal injury and leukocyte infiltration elicited by indomethacin. [ ADR Type 1 ] | Role of intercellular adhesion molecule 1 in indomethacin-induced ileitis
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| Gastric Damage | Myeloperoxidase precursor (P05164) | Treatment with thalidomide@ dexamethasone@ or fucoidin reduced gastric damage and MPO activity induced by indomethacin. After indomethacin administration@ TNF-R1-/- had less gastric damage and MPO activity than controls. [ ADR Type 1 ] | Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice
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| Gastric Damage | Nitric oxide synthase inducible (P35228) | Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice. [ ADR Type 1 ] | Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice
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| Gastric Damage | Tumor necrosis factor precursor (P01375) | TNF-alpha, acting via TNF-R1, is involved in indomethacin induced gastric damage and granulocyte infiltration. [ ADR Type 1 ] | Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice
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| Gastric Damage | Tumor necrosis factor receptor superfamily member 1A (TNF-R1) (P19438) | Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice [ ADR Type 1 ] | Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice
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| Gastropathy | CD18 (P32592) | Indomethacin induced gastropathy in CD18@ intercellular adhesion molecule 1@ or P-selectin deficient mice [ ADR Type 3 ] | Indomethacin induced gastropathy in CD18, intercellular adhesion molecule 1, or P-selectin deficient mice Gut
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| Gastropathy | Intercellular adhesion molecule 1 precursor (P05362) | Indomethacin induced gastropathy in CD18@ intercellular adhesion molecule 1@ or P-selectin deficient mice. [ ADR Type 3 ] | Indomethacin induced gastropathy in CD18, intercellular adhesion molecule 1, or P-selectin deficient mice Gut
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| Gastropathy | P-selectin (P16109) | Indomethacin induced gastropathy in CD18@ intercellular adhesion molecule 1@ or P-selectin deficient mice [ ADR Type 3 ] | Indomethacin induced gastropathy in CD18, intercellular adhesion molecule 1, or P-selectin deficient mice Gut
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| Granulocyte Infiltration | Myeloperoxidase precursor (P05164) | Treatment with thalidomide@ dexamethasone@ or fucoidin reduced gastric damage and MPO activity induced by indomethacin. After indomethacin administration@ TNF-R1-/- had less gastric damage and MPO activity than controls. [ ADR Type 1 ] | Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice
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| Granulocyte Infiltration | Nitric oxide synthase inducible (P35228) | Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice. [ ADR Type 1 ] | Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice
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| Granulocyte Infiltration | Tumor necrosis factor precursor (P01375) | TNF-alpha, acting via TNF-R1, is involved in indomethacin induced gastric damage and granulocyte infiltration. [ ADR Type 1 ] | Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice
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| Granulocyte Infiltration | Tumor necrosis factor receptor superfamily member 1A (TNF-R1) (P19438) | Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice [ ADR Type 1 ] | Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice
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| Inhibition Of Endothelial Cell Proliferation | retinoblastoma protein (PRb) (P06400) | Indomethacin inhibits endothelial cell proliferation by suppressing cell cycle proteins and PRB phosphorylation@suggestting that indomethacin arrests endothelial cell proliferation essential for angiogenesis by modulating cell cycle protein levels. [ ADR Type 2 ] | Release of calcitonin gene-related peptide (CGRP) from guinea pig dura mater in vitro is inhibited by sumatriptan but unaffected by nitric oxide
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| Selective Effect Of A P-Chlorophenyl Moiety | Cytochrome b5 (Q9V4N3) | Indomethacin in vitro also caused a loss of cytochrome b5@ NADH-cytochrome b5 reductase@ NADPH-cytochrome c reductase and Epoxide hydrolase activities@ but an activation of UDP-glucuronyltransferase@which leads to selective effect of a p-chlorophenyl moiety [ ADR Type 1 ] | Denaturation of cytochrome P-450 by indomethacin and other non-steroidal anti-inflammatory drugs: evidence for a surfactant mechanism and a selective effect of a p-chlorophenyl moiety
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| Selective Effect Of A P-Chlorophenyl Moiety | Cytochrome P450 reductase (P16435) | Indomethacin in vitro also caused a loss of cytochrome b5@ NADH-cytochrome b5 reductase@ NADPH-cytochrome c reductase and Epoxide hydrolase activities@ but an activation of UDP-glucuronyltransferase@which leads to selective effect of a p-chlorophenyl moiety. [ ADR Type 1 ] | Denaturation of cytochrome P-450 by indomethacin and other non-steroidal anti-inflammatory drugs: evidence for a surfactant mechanism and a selective effect of a p-chlorophenyl moiety
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| Selective Effect Of A P-Chlorophenyl Moiety | Epoxide hydrolase (P07099) | Indomethacin in vitro also caused a loss of cytochrome b5@ NADH-cytochrome b5 reductase@ NADPH-cytochrome c reductase and Epoxide hydrolase activities@ but an activation of UDP-glucuronyltransferase@which leads to selective effect of a p-chlorophenyl moiety. [ ADR Type 1 ] | Denaturation of cytochrome P-450 by indomethacin and other non-steroidal anti-inflammatory drugs: evidence for a surfactant mechanism and a selective effect of a p-chlorophenyl moiety
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| Selective Effect Of A P-Chlorophenyl Moiety | NADH-cytochrome b5 reductase (P00387) | Indomethacin in vitro also caused a loss of cytochrome b5, NADH-cytochrome b5 reductase, NADPH-cytochrome c reductase and epoxide hydrolase activities, but an activation of UDP-glucuronyltransferase,which leads to selective effect of a p-chlorophenyl moiety [ ADR Type 1 ] | Denaturation of cytochrome P-450 by indomethacin and other non-steroidal anti-inflammatory drugs: evidence for a surfactant mechanism and a selective effect of a p-chlorophenyl moiety
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| Selective Effect Of A P-Chlorophenyl Moiety | UDP-glucuronyltransferase (Q64550) | Indomethacin in vitro also caused a loss of cytochrome b5@ NADH-cytochrome b5 reductase@ NADPH-cytochrome c reductase and epoxide hydrolase activities@ but an activation of UDP-glucuronyltransferase@which leads to selective effect of a p-chlorophenyl moiety [ ADR Type 1 ] | Denaturation of cytochrome P-450 by indomethacin and other non-steroidal anti-inflammatory drugs: evidence for a surfactant mechanism and a selective effect of a p-chlorophenyl moiety
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