| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T270 |
0-200 |
Sentence |
denotes |
MLN4760 is a potent and selective human ACE2 inhibitor (IC50 = 0.44 nM against soluble human ACE2) whose synthesis produces a racemic mixture of two diastereomers that showed 75:25 ratio for Isomer A: |
| T271 |
201-310 |
Sentence |
denotes |
Isomer B [113,114] and the purified isomer B is the isomer commercially available from Merck Millipore [114]. |
| T272 |
311-496 |
Sentence |
denotes |
Testing MLN-4760 racemic mixture and its isomers, it was observed a concentration-dependent inhibition of recombinant human (rh)ACE or rhACE2 activities with all three inhibitors [114]. |
| T273 |
497-847 |
Sentence |
denotes |
The isomer B was less selective (near minimal-maximal rhACE inhibition range 10−6M-10−4M) than the racemate or the isomer A (near minimal-maximal rhACE inhibition range 10−6M-10−2M) and less effective (near maximal rhACE2 inhibition at 10−7M) than the racemate or the isomer A (near maximal rhACE2 inhibition at 10−8 M) for rhACE2 versus rhACE [114]. |
| T274 |
848-1214 |
Sentence |
denotes |
Moreover, all three inhibitors exerted a significantly higher inhibitory activity against soluble than membrane-bound forms of (m)ACE2 (near maximal mACE2 inhibition at 10−6M), being the isomer B more selective and effective than the racemate or the isomer A for mACE2 vs. mACE expressed on the surface of mononuclear cells (or CD34 hematopoietic progenitors) [114]. |
| T275 |
1215-1314 |
Sentence |
denotes |
A second ACE2 inhibitor, Dx600, produced similar results to those obtained with the isomer B [114]. |
| T276 |
1315-1481 |
Sentence |
denotes |
Another study evaluated the inhibitory activity of both MLN-4760 and DX600 (either the linear conformational form or the disulfide bridged cyclic variant) inhibitors. |
| T277 |
1482-1693 |
Sentence |
denotes |
In this report, the experiments were performed at pH 6.5 [115], a pH at which rhACE2 proteolysis operates at maximal activity [79] and a condition that resembles hypercapnic acidosis which may occur during SARS. |
| T278 |
1694-2030 |
Sentence |
denotes |
MLN-4760 was still able to strongly and specifically inhibit rhACE2 activity (near maximal inhibition at 10−8 M), preventing rhACE2-driven Ang II degradation into Ang (1–7), whereas DX600 (either linear or cyclic variant) inhibits rhACE2 at relatively higher concentration (near maximal inhibition at 10−6 M–10−7 M, respectively) [115]. |
| T279 |
2031-2175 |
Sentence |
denotes |
Altogether these data indicate that the racemate or the isomer A are more effective in inhibiting soluble forms of ACE2 than isomer B and Dx600. |
| T280 |
2176-2529 |
Sentence |
denotes |
Therefore, these inhibitors at opportune (low) concentrations are expected to preferentially reduce systemic sACE2 activity, while preserving the ACE2 activity of (local) membrane-associated forms of ACE2, knowing that catalytic activity of circulating ACE2 was undetectable in human plasma of healthy subjects due to an endogenous ACE2 inhibitor [116]. |
