LitCovid-sentences  

PMC:7600245 / 38469-42003 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T288 0-4 Sentence denotes 4.1.
T289 5-31 Sentence denotes Selinexor (Xpovio, KPT330)
T290 32-128 Sentence denotes Selinexor is bis(trifluoromethyl)phenyl-triazole-based antineoplastic small molecule (Figure 7).
T291 129-170 Sentence denotes It was first approved in 2019 by the U.S.
T292 171-262 Sentence denotes FDA and is being prescribed with dexamethasone for refractory or relapsed multiple myeloma.
T293 263-404 Sentence denotes Selinexor is an orally bioavailable, selective inhibitor of chromosome region maintenance 1 (CRM1) protein (also known as exportin 1 (XPO1)).
T294 405-531 Sentence denotes CRM1 is the main export factor that shuttles nuclear proteins to the cytoplasm and is typically overexpressed in cancer cells.
T295 532-656 Sentence denotes Its selective inhibition can assist in restoring the endogenous tumor-suppressing processes so as to eliminate cancer cells.
T296 657-940 Sentence denotes 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.
T297 941-1016 Sentence denotes This leads to the accumulation of tumor suppressor proteins in the nucleus.
T298 1017-1168 Sentence denotes It also results in decreased levels of oncoproteins, cell cycle arrest, and apoptosis of cancer cells without affecting the normal cells [119,120,121].
T299 1169-1419 Sentence denotes Considering 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.
T300 1420-1524 Sentence denotes Thus, the CRM1 inhibitor selinexor may exert relevant antiviral and anti-inflammatory effects [122,123].
T301 1525-1693 Sentence denotes In fact, CRM1 inhibitors have exhibited activity against >20 different viruses, including RNA viruses such as respiratory syncytial virus and influenza virus [122,123].
T302 1694-1821 Sentence denotes Furthermore, CRM1 inhibition has also been identified in in vitro assays to have a potential activity against SARS-CoV-2 [124].
T303 1822-1942 Sentence denotes CRM1 was found to contribute to exporting several SARS-CoV proteins, such as S, N, 9b, Orf3 and Orf6 out of the nucleus.
T304 1943-2029 Sentence denotes Thus, CRM1 inhibition is expected to inhibit the viral assembly [125,126,127,128,129].
T305 2030-2211 Sentence denotes Moreover, CRM1 has also been found to contribute to the nuclear export and functional inactivation of antioxidant, anti-inflammatory, and cytoprotective transcription factors [130].
T306 2212-2354 Sentence denotes High levels of CRM1 are found in multiple inflammatory conditions and may magnify inflammatory responses leading to severe organ damage [131].
T307 2355-2565 Sentence denotes 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.
T308 2566-2673 Sentence denotes For example, in a mouse model of sepsis, selinexor increased survival following a lethal dose of endotoxin.
T309 2674-2859 Sentence denotes 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.
T310 2860-2985 Sentence denotes Selinexor also mitigated lipopolysaccharide-induced lung injury that is similar to acute respiratory distress syndrome [132].
T311 2986-3101 Sentence denotes Currently, selinexor is being evaluated in at least two phase 2 randomized trials in the U.S. in COVID-19 patients.
T312 3102-3534 Sentence denotes 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).