LitCovid-sentences  

PMC:7408073 / 98067-101487 JSONTXT 11 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T477 0-671 Sentence denotes Briefly, one of the best candidates to treat COVID-19 patients, but not to prevent viral entry, is the small synthetic molecule MLN-4760 (specific ACE2 inhibitor, also known as C16, GL1001 or ORE1001, [113]) for the following reasons:(1) It has been shown to bind/inhibit ACE2 enzymatic activity even at low/acidic pH (pH 6.5, [115]) typical of hypercapnia (as it might occur in lungs of COVID-19 patients) when human ACE2 activity is maximal [79]; nevertheless, it retains its inhibitory effects on soluble ACE2 bound to spike proteins [24], indicating that it is able to bind and inhibit ACE2 activity regardless ACE2 binding to SARS-CoV-2 particles or to S1 fragments.
T478 672-1076 Sentence denotes (2) No significant adverse effects were described upon its chronic administration neither alone nor in combination with ACE2 activators (while inhibiting their activating effects) nor after inducing functional impairment of ACE2 activity in rodent experiments in vivo [52,117,118,122,183,184] nor in a clinical Phase I trial in humans (http://oreholdings.com/wp-content/uploads/2013/06/09.10.09-425.pdf);
T479 1077-1159 Sentence denotes (3) Its administration by different route is well described in rodents and humans.
T480 1160-1510 Sentence denotes In particular:(a) Chronic administration (about 4 weeks) of C-16/DLM-4760 in combination with ACE2 activating treatments was performed by daily intraperitoneal injection at a dose of 25mg/kg in distilled water (as a solution of 42 mg/mL) or 0.9% sterile saline (as a solution of 84 mg/mL using a 0.5-mL insulin syringe) freshly prepared [52,183,184].
T481 1511-1842 Sentence denotes (b) Alternatively, chronic administration (about 8 days) of GL1001/DLM-4760 disodium salt in combination with an ACE2 activating treatment was performed by subcutaneous injection (5mL/kg) containing up to a dose of 300 mg/kg, twice a day, formulated in a vehicle solution [15% 2-hydroxypropyl-β-cyclodextrin (HPBDC)/85% H2O] [122].
T482 1843-1928 Sentence denotes Subchronic doses of GL1001 indicate no adverse effects up to 1,000 mg/kg (see [122]).
T483 1929-2018 Sentence denotes (c) In humans ORE1001/GL1001/MLN-4760 was already proposed and tested in clinical trials.
T484 2019-2187 Sentence denotes Its pharmaceutical indication was for digestive tract inflammations (Inflammatory bowel disease, gastritis and colitis) that are correlated with overexpression of ACE2.
T485 2188-2264 Sentence denotes In a Phase I clinical testing up 14 days dosing, ORE1001 was well tolerated.
T486 2265-2349 Sentence denotes Subjects received drug (dosing up to 2100 mg) with no side adverse effects reported.
T487 2350-2487 Sentence denotes In particular, 47 subjects received single-dose from 2.1 to 2100 mg and 24 subjects received 14 day multiple doses from 50 mg to 1800 mg.
T488 2488-2577 Sentence denotes All doses were well tolerated, with no significant side effects including blood pressure.
T489 2578-2735 Sentence denotes Pharmacokinetics of orally administered capsules was consistent with once-daily dosing. (http://oreholdings.com/wp-content/uploads/2013/06/09.10.09-425.pdf).
T490 2736-2894 Sentence denotes 300 mg (active drug) oral capsules were used in a Phase Ib/IIa clinical trial that was, however, abandoned. (https://clinicaltrials.gov/ct2/show/NCT01039597).
T491 2895-3044 Sentence denotes (d) Finally, MLN-4760 was also administered (2.5 mg/kg per day) by nasal inhalation for 2–3 days in lung-infected mice by Pseudomonas bacteria [185].
T492 3045-3186 Sentence denotes Interestingly, the report underscores the role played by local concentration of molecules (ACE2) in modulating lung inflammation and disease.
T493 3187-3420 Sentence denotes For these reasons, in diseases involving respiratory tract, like SARS, inhalation treatment is preferable, even for the lower concentration (and hopefully lower toxicity) of MLN-4760 needed for this route of treatment administration.