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LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T6","span":{"begin":2335,"end":2340},"obj":"Body_part"},{"id":"T7","span":{"begin":2841,"end":2858},"obj":"Body_part"},{"id":"T8","span":{"begin":2912,"end":2916},"obj":"Body_part"}],"attributes":[{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/UBERON_0000062"},{"id":"A7","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/UBERON_0001179"},{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"4.1. Selinexor (Xpovio, KPT330)\nSelinexor is bis(trifluoromethyl)phenyl-triazole-based antineoplastic small molecule (Figure 7). It was first approved in 2019 by the U.S. FDA and is being prescribed with dexamethasone for refractory or relapsed multiple myeloma. Selinexor is an orally bioavailable, selective inhibitor of chromosome region maintenance 1 (CRM1) protein (also known as exportin 1 (XPO1)). CRM1 is the main export factor that shuttles nuclear proteins to the cytoplasm and is typically overexpressed in cancer cells. Its selective inhibition can assist in restoring the endogenous tumor-suppressing processes so as to eliminate cancer cells. Specifically, selinexor selectively and irreversibly modifies the essential Cys528 residue in CRM1, and thus, it blocks CRM1-mediated nuclear export of cargo proteins such as tumor suppressor proteins (p21, p53, pRB, BRCA1/2, FOXO, and others) from the cell nucleus to the cytoplasm. This leads to the accumulation of tumor suppressor proteins in the nucleus. It also results in decreased levels of oncoproteins, cell cycle arrest, and apoptosis of cancer cells without affecting the normal cells [119,120,121].\nConsidering the current viral pandemic, CRM1 has been put forward as a facilitator of the export of viral proteins from the nucleus of the host cell to the cytoplasm as well as an amplifier of the activities of pro-inflammatory transcription factors. Thus, the CRM1 inhibitor selinexor may exert relevant antiviral and anti-inflammatory effects [122,123]. In fact, CRM1 inhibitors have exhibited activity against \u003e20 different viruses, including RNA viruses such as respiratory syncytial virus and influenza virus [122,123]. Furthermore, CRM1 inhibition has also been identified in in vitro assays to have a potential activity against SARS-CoV-2 [124]. CRM1 was found to contribute to exporting several SARS-CoV proteins, such as S, N, 9b, Orf3 and Orf6 out of the nucleus. Thus, CRM1 inhibition is expected to inhibit the viral assembly [125,126,127,128,129]. Moreover, CRM1 has also been found to contribute to the nuclear export and functional inactivation of antioxidant, anti-inflammatory, and cytoprotective transcription factors [130]. High levels of CRM1 are found in multiple inflammatory conditions and may magnify inflammatory responses leading to severe organ damage [131]. In this direction, selinexor and similar inhibitors have exhibited potent anti-inflammatory activity by suppressing the activation of NFkB and p38 signaling, leading to reduced cytokines in a variety of models. For example, in a mouse model of sepsis, selinexor increased survival following a lethal dose of endotoxin. Selinexor reduced the inflammatory cytokine secretion of IL-6, TNF-α, and HMGB1 while reducing the numbers of macrophage and polymorphonuclear neutrophils in the mice peritoneal cavity. Selinexor also mitigated lipopolysaccharide-induced lung injury that is similar to acute respiratory distress syndrome [132].\nCurrently, selinexor is being evaluated in at least two phase 2 randomized trials in the U.S. in COVID-19 patients. One is to evaluate the activity, safety and reduction in mortality of two regimens of low-dose selinexor in patients with moderate or severe COVID-19 (NCT04355676, n = 80) and the other is to evaluate the activity of low-dose selinexor and its effect on the clinical recovery, viral load, length of hospitalization, and rate of morbidity and mortality in participants with severe COVID-19 compared to placebo (NCT04349098, n = 230)."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T51","span":{"begin":791,"end":805},"obj":"http://purl.obolibrary.org/obo/GO_0051168"},{"id":"T52","span":{"begin":832,"end":848},"obj":"http://purl.obolibrary.org/obo/GO_0051726"},{"id":"T53","span":{"begin":975,"end":991},"obj":"http://purl.obolibrary.org/obo/GO_0051726"},{"id":"T54","span":{"begin":1070,"end":1087},"obj":"http://purl.obolibrary.org/obo/GO_0007050"},{"id":"T55","span":{"begin":1070,"end":1080},"obj":"http://purl.obolibrary.org/obo/GO_0007049"},{"id":"T56","span":{"begin":1093,"end":1102},"obj":"http://purl.obolibrary.org/obo/GO_0097194"},{"id":"T57","span":{"begin":1093,"end":1102},"obj":"http://purl.obolibrary.org/obo/GO_0006915"},{"id":"T58","span":{"begin":1397,"end":1418},"obj":"http://purl.obolibrary.org/obo/GO_0000981"},{"id":"T59","span":{"begin":1397,"end":1410},"obj":"http://purl.obolibrary.org/obo/GO_0006351"},{"id":"T60","span":{"begin":1992,"end":2006},"obj":"http://purl.obolibrary.org/obo/GO_0019068"},{"id":"T61","span":{"begin":2086,"end":2100},"obj":"http://purl.obolibrary.org/obo/GO_0051168"},{"id":"T62","span":{"begin":2183,"end":2204},"obj":"http://purl.obolibrary.org/obo/GO_0000981"},{"id":"T63","span":{"begin":2183,"end":2196},"obj":"http://purl.obolibrary.org/obo/GO_0006351"},{"id":"T64","span":{"begin":2294,"end":2316},"obj":"http://purl.obolibrary.org/obo/GO_0006954"},{"id":"T65","span":{"begin":2502,"end":2511},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T66","span":{"begin":2709,"end":2727},"obj":"http://purl.obolibrary.org/obo/GO_0001816"},{"id":"T67","span":{"begin":2718,"end":2727},"obj":"http://purl.obolibrary.org/obo/GO_0046903"}],"text":"4.1. Selinexor (Xpovio, KPT330)\nSelinexor is bis(trifluoromethyl)phenyl-triazole-based antineoplastic small molecule (Figure 7). It was first approved in 2019 by the U.S. FDA and is being prescribed with dexamethasone for refractory or relapsed multiple myeloma. Selinexor is an orally bioavailable, selective inhibitor of chromosome region maintenance 1 (CRM1) protein (also known as exportin 1 (XPO1)). CRM1 is the main export factor that shuttles nuclear proteins to the cytoplasm and is typically overexpressed in cancer cells. Its selective inhibition can assist in restoring the endogenous tumor-suppressing processes so as to eliminate cancer cells. Specifically, selinexor selectively and irreversibly modifies the essential Cys528 residue in CRM1, and thus, it blocks CRM1-mediated nuclear export of cargo proteins such as tumor suppressor proteins (p21, p53, pRB, BRCA1/2, FOXO, and others) from the cell nucleus to the cytoplasm. This leads to the accumulation of tumor suppressor proteins in the nucleus. It also results in decreased levels of oncoproteins, cell cycle arrest, and apoptosis of cancer cells without affecting the normal cells [119,120,121].\nConsidering the current viral pandemic, CRM1 has been put forward as a facilitator of the export of viral proteins from the nucleus of the host cell to the cytoplasm as well as an amplifier of the activities of pro-inflammatory transcription factors. Thus, the CRM1 inhibitor selinexor may exert relevant antiviral and anti-inflammatory effects [122,123]. In fact, CRM1 inhibitors have exhibited activity against \u003e20 different viruses, including RNA viruses such as respiratory syncytial virus and influenza virus [122,123]. Furthermore, CRM1 inhibition has also been identified in in vitro assays to have a potential activity against SARS-CoV-2 [124]. CRM1 was found to contribute to exporting several SARS-CoV proteins, such as S, N, 9b, Orf3 and Orf6 out of the nucleus. Thus, CRM1 inhibition is expected to inhibit the viral assembly [125,126,127,128,129]. Moreover, CRM1 has also been found to contribute to the nuclear export and functional inactivation of antioxidant, anti-inflammatory, and cytoprotective transcription factors [130]. High levels of CRM1 are found in multiple inflammatory conditions and may magnify inflammatory responses leading to severe organ damage [131]. In this direction, selinexor and similar inhibitors have exhibited potent anti-inflammatory activity by suppressing the activation of NFkB and p38 signaling, leading to reduced cytokines in a variety of models. For example, in a mouse model of sepsis, selinexor increased survival following a lethal dose of endotoxin. Selinexor reduced the inflammatory cytokine secretion of IL-6, TNF-α, and HMGB1 while reducing the numbers of macrophage and polymorphonuclear neutrophils in the mice peritoneal cavity. Selinexor also mitigated lipopolysaccharide-induced lung injury that is similar to acute respiratory distress syndrome [132].\nCurrently, selinexor is being evaluated in at least two phase 2 randomized trials in the U.S. in COVID-19 patients. One is to evaluate the activity, safety and reduction in mortality of two regimens of low-dose selinexor in patients with moderate or severe COVID-19 (NCT04355676, n = 80) and the other is to evaluate the activity of low-dose selinexor and its effect on the clinical recovery, viral load, length of hospitalization, and rate of morbidity and mortality in participants with severe COVID-19 compared to placebo (NCT04349098, n = 230)."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T18","span":{"begin":245,"end":261},"obj":"Phenotype"},{"id":"T19","span":{"begin":518,"end":524},"obj":"Phenotype"},{"id":"T20","span":{"begin":596,"end":601},"obj":"Phenotype"},{"id":"T21","span":{"begin":643,"end":649},"obj":"Phenotype"},{"id":"T22","span":{"begin":832,"end":837},"obj":"Phenotype"},{"id":"T23","span":{"begin":975,"end":980},"obj":"Phenotype"},{"id":"T24","span":{"begin":1106,"end":1112},"obj":"Phenotype"},{"id":"T25","span":{"begin":2599,"end":2605},"obj":"Phenotype"},{"id":"T26","span":{"begin":2949,"end":2969},"obj":"Phenotype"}],"attributes":[{"id":"A18","pred":"hp_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/HP_0006775"},{"id":"A19","pred":"hp_id","subj":"T19","obj":"http://purl.obolibrary.org/obo/HP_0002664"},{"id":"A20","pred":"hp_id","subj":"T20","obj":"http://purl.obolibrary.org/obo/HP_0002664"},{"id":"A21","pred":"hp_id","subj":"T21","obj":"http://purl.obolibrary.org/obo/HP_0002664"},{"id":"A22","pred":"hp_id","subj":"T22","obj":"http://purl.obolibrary.org/obo/HP_0002664"},{"id":"A23","pred":"hp_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/HP_0002664"},{"id":"A24","pred":"hp_id","subj":"T24","obj":"http://purl.obolibrary.org/obo/HP_0002664"},{"id":"A25","pred":"hp_id","subj":"T25","obj":"http://purl.obolibrary.org/obo/HP_0100806"},{"id":"A26","pred":"hp_id","subj":"T26","obj":"http://purl.obolibrary.org/obo/HP_0002098"}],"text":"4.1. Selinexor (Xpovio, KPT330)\nSelinexor is bis(trifluoromethyl)phenyl-triazole-based antineoplastic small molecule (Figure 7). It was first approved in 2019 by the U.S. FDA and is being prescribed with dexamethasone for refractory or relapsed multiple myeloma. Selinexor is an orally bioavailable, selective inhibitor of chromosome region maintenance 1 (CRM1) protein (also known as exportin 1 (XPO1)). CRM1 is the main export factor that shuttles nuclear proteins to the cytoplasm and is typically overexpressed in cancer cells. Its selective inhibition can assist in restoring the endogenous tumor-suppressing processes so as to eliminate cancer cells. Specifically, selinexor selectively and irreversibly modifies the essential Cys528 residue in CRM1, and thus, it blocks CRM1-mediated nuclear export of cargo proteins such as tumor suppressor proteins (p21, p53, pRB, BRCA1/2, FOXO, and others) from the cell nucleus to the cytoplasm. This leads to the accumulation of tumor suppressor proteins in the nucleus. It also results in decreased levels of oncoproteins, cell cycle arrest, and apoptosis of cancer cells without affecting the normal cells [119,120,121].\nConsidering the current viral pandemic, CRM1 has been put forward as a facilitator of the export of viral proteins from the nucleus of the host cell to the cytoplasm as well as an amplifier of the activities of pro-inflammatory transcription factors. Thus, the CRM1 inhibitor selinexor may exert relevant antiviral and anti-inflammatory effects [122,123]. In fact, CRM1 inhibitors have exhibited activity against \u003e20 different viruses, including RNA viruses such as respiratory syncytial virus and influenza virus [122,123]. Furthermore, CRM1 inhibition has also been identified in in vitro assays to have a potential activity against SARS-CoV-2 [124]. CRM1 was found to contribute to exporting several SARS-CoV proteins, such as S, N, 9b, Orf3 and Orf6 out of the nucleus. Thus, CRM1 inhibition is expected to inhibit the viral assembly [125,126,127,128,129]. Moreover, CRM1 has also been found to contribute to the nuclear export and functional inactivation of antioxidant, anti-inflammatory, and cytoprotective transcription factors [130]. High levels of CRM1 are found in multiple inflammatory conditions and may magnify inflammatory responses leading to severe organ damage [131]. In this direction, selinexor and similar inhibitors have exhibited potent anti-inflammatory activity by suppressing the activation of NFkB and p38 signaling, leading to reduced cytokines in a variety of models. For example, in a mouse model of sepsis, selinexor increased survival following a lethal dose of endotoxin. Selinexor reduced the inflammatory cytokine secretion of IL-6, TNF-α, and HMGB1 while reducing the numbers of macrophage and polymorphonuclear neutrophils in the mice peritoneal cavity. Selinexor also mitigated lipopolysaccharide-induced lung injury that is similar to acute respiratory distress syndrome [132].\nCurrently, selinexor is being evaluated in at least two phase 2 randomized trials in the U.S. in COVID-19 patients. One is to evaluate the activity, safety and reduction in mortality of two regimens of low-dose selinexor in patients with moderate or severe COVID-19 (NCT04355676, n = 80) and the other is to evaluate the activity of low-dose selinexor and its effect on the clinical recovery, viral load, length of hospitalization, and rate of morbidity and mortality in participants with severe COVID-19 compared to placebo (NCT04349098, n = 230)."}

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T288","span":{"begin":0,"end":4},"obj":"Sentence"},{"id":"T289","span":{"begin":5,"end":31},"obj":"Sentence"},{"id":"T290","span":{"begin":32,"end":128},"obj":"Sentence"},{"id":"T291","span":{"begin":129,"end":170},"obj":"Sentence"},{"id":"T292","span":{"begin":171,"end":262},"obj":"Sentence"},{"id":"T293","span":{"begin":263,"end":404},"obj":"Sentence"},{"id":"T294","span":{"begin":405,"end":531},"obj":"Sentence"},{"id":"T295","span":{"begin":532,"end":656},"obj":"Sentence"},{"id":"T296","span":{"begin":657,"end":940},"obj":"Sentence"},{"id":"T297","span":{"begin":941,"end":1016},"obj":"Sentence"},{"id":"T298","span":{"begin":1017,"end":1168},"obj":"Sentence"},{"id":"T299","span":{"begin":1169,"end":1419},"obj":"Sentence"},{"id":"T300","span":{"begin":1420,"end":1524},"obj":"Sentence"},{"id":"T301","span":{"begin":1525,"end":1693},"obj":"Sentence"},{"id":"T302","span":{"begin":1694,"end":1821},"obj":"Sentence"},{"id":"T303","span":{"begin":1822,"end":1942},"obj":"Sentence"},{"id":"T304","span":{"begin":1943,"end":2029},"obj":"Sentence"},{"id":"T305","span":{"begin":2030,"end":2211},"obj":"Sentence"},{"id":"T306","span":{"begin":2212,"end":2354},"obj":"Sentence"},{"id":"T307","span":{"begin":2355,"end":2565},"obj":"Sentence"},{"id":"T308","span":{"begin":2566,"end":2673},"obj":"Sentence"},{"id":"T309","span":{"begin":2674,"end":2859},"obj":"Sentence"},{"id":"T310","span":{"begin":2860,"end":2985},"obj":"Sentence"},{"id":"T311","span":{"begin":2986,"end":3101},"obj":"Sentence"},{"id":"T312","span":{"begin":3102,"end":3534},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"4.1. Selinexor (Xpovio, KPT330)\nSelinexor is bis(trifluoromethyl)phenyl-triazole-based antineoplastic small molecule (Figure 7). It was first approved in 2019 by the U.S. FDA and is being prescribed with dexamethasone for refractory or relapsed multiple myeloma. Selinexor is an orally bioavailable, selective inhibitor of chromosome region maintenance 1 (CRM1) protein (also known as exportin 1 (XPO1)). CRM1 is the main export factor that shuttles nuclear proteins to the cytoplasm and is typically overexpressed in cancer cells. Its selective inhibition can assist in restoring the endogenous tumor-suppressing processes so as to eliminate cancer cells. Specifically, selinexor selectively and irreversibly modifies the essential Cys528 residue in CRM1, and thus, it blocks CRM1-mediated nuclear export of cargo proteins such as tumor suppressor proteins (p21, p53, pRB, BRCA1/2, FOXO, and others) from the cell nucleus to the cytoplasm. This leads to the accumulation of tumor suppressor proteins in the nucleus. It also results in decreased levels of oncoproteins, cell cycle arrest, and apoptosis of cancer cells without affecting the normal cells [119,120,121].\nConsidering the current viral pandemic, CRM1 has been put forward as a facilitator of the export of viral proteins from the nucleus of the host cell to the cytoplasm as well as an amplifier of the activities of pro-inflammatory transcription factors. Thus, the CRM1 inhibitor selinexor may exert relevant antiviral and anti-inflammatory effects [122,123]. In fact, CRM1 inhibitors have exhibited activity against \u003e20 different viruses, including RNA viruses such as respiratory syncytial virus and influenza virus [122,123]. Furthermore, CRM1 inhibition has also been identified in in vitro assays to have a potential activity against SARS-CoV-2 [124]. CRM1 was found to contribute to exporting several SARS-CoV proteins, such as S, N, 9b, Orf3 and Orf6 out of the nucleus. Thus, CRM1 inhibition is expected to inhibit the viral assembly [125,126,127,128,129]. Moreover, CRM1 has also been found to contribute to the nuclear export and functional inactivation of antioxidant, anti-inflammatory, and cytoprotective transcription factors [130]. High levels of CRM1 are found in multiple inflammatory conditions and may magnify inflammatory responses leading to severe organ damage [131]. In this direction, selinexor and similar inhibitors have exhibited potent anti-inflammatory activity by suppressing the activation of NFkB and p38 signaling, leading to reduced cytokines in a variety of models. For example, in a mouse model of sepsis, selinexor increased survival following a lethal dose of endotoxin. Selinexor reduced the inflammatory cytokine secretion of IL-6, TNF-α, and HMGB1 while reducing the numbers of macrophage and polymorphonuclear neutrophils in the mice peritoneal cavity. Selinexor also mitigated lipopolysaccharide-induced lung injury that is similar to acute respiratory distress syndrome [132].\nCurrently, selinexor is being evaluated in at least two phase 2 randomized trials in the U.S. in COVID-19 patients. One is to evaluate the activity, safety and reduction in mortality of two regimens of low-dose selinexor in patients with moderate or severe COVID-19 (NCT04355676, n = 80) and the other is to evaluate the activity of low-dose selinexor and its effect on the clinical recovery, viral load, length of hospitalization, and rate of morbidity and mortality in participants with severe COVID-19 compared to placebo (NCT04349098, n = 230)."}

LitCovid-PubTator

PMC:7600245 / 38469-42003 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7600245 / 38469-42003 JSON TXT