PMC:7408073 / 59774-61651 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7408073","sourcedb":"PMC","sourceid":"7408073","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7408073","text":"Extensive experiments have been also performed with DX600, a specific peptide ACE2 inhibitor that exhibited a mixed competitive and non-competitive type of inhibition [120]. Actually, several reports describing Dx600 inhibitor administration in mice suggest its safe use. Of interest, a report described its (safe) use alone (1 mg/kg per day) by nasal inhalation for 3 days in a mouse model of endotoxin-induced lung inflammation [121]; however, this inhibitor is less efficacious than MLN-4760 in inhibiting the soluble forms of human rACE2 [114,115]. Altogether these reports on administration of ACE2 inhibitors do not reveal significant adverse impacts or mortality in experimental animals, which suggests their safety in chronic administration. This was also confirmed in human clinical trials with MLN-4760 (clinical name: ORE1001, see later). Of interest, a report showed that on day 28 post-myocardial infarction, adult male Sprague-Dawley rats that had received MLN-4760 (also called C16) 25 mg/mL/day by daily intraperitoneal injection (as a solution of 42 mg/mL in distilled water) tended to have lower left ventricular pulse pressure, mean arterial pressures and left ventricular relaxation time constant-Tau compared to untreated group (see table 2 of the paper) [52], suggesting a possible protective role of ACE2 inhibition in post-myocardial infarction. Therefore, MLN-4760 might be helpful not only for COVID-19 but also in targeted therapies for pathologies correlated with an excessive increase of ACE2 activity that may involve heart, lung, liver, colon or other tissues/organs expressing ACE2 such as blood and endothelial cells. As an example, GL1001 (old name of MLN-4760) showed to produce an anti-inflammatory activity in a mouse model of colitis [122], highlighting the importance of the yin-yang balance of ACE/ACE2 pathways (“in medio stat 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