MLN-4760 manufacturers
- MLN-4760
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- $187.00 / 1mg
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2024-11-19
- CAS:305335-31-3
- Min. Order:
- Purity: 99.05%
- Supply Ability: 10g
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| | MLN-4760 Basic information |
| Product Name: | MLN-4760 | | Synonyms: | MLN-4760;L-Histidine, N-[(1S)-1-carboxy-3-methylbutyl]-3-[(3,5-dichlorophenyl)methyl]-;((S)-1-carboxy-2-(1-(3,5-dichlorobenzyl)-1H-imidazol-5-yl)ethyl)-L-leucine;inhibit,Angiotensin-converting Enzyme (ACE),MLN 4760,Inhibitor,MLN-4760,MLN4760;(2S)-2-{[(1S)-1-carboxy-2-{1-[(3,5-dichlorophenyl)methyl]-1H-imidazol-5-yl}ethyl]amino}-4-methylpentanoic acid | | CAS: | 305335-31-3 | | MF: | C19H23Cl2N3O4 | | MW: | 428.31 | | EINECS: | | | Product Categories: | | | Mol File: | 305335-31-3.mol |  |
| | MLN-4760 Chemical Properties |
| storage temp. | Store at -20°C | | solubility | DMSO: soluble | | form | A solid | | color | Off-white to light yellow |
| | MLN-4760 Usage And Synthesis |
| Definition | ChEBI: MLN-4760 is a L-histidine derivative that is L-histidine in which a hydrogen of the primary amino group is substituted by a (1S)-1-carboxy-3-methylbutyl group and the ring NH group is substituted by a 3,5-dichlorobenzyl group. It is a potent and selective human angiotensin-converting enzyme 2 (ACE2) inhibitor (IC50 = 0.44 nM) which was in clinical development for the treatment of ulcerative colitis. It has a role as an anti-inflammatory agent and an EC 3.4.17.23 (angiotensin-converting enzyme 2) inhibitor. It is a L-histidine derivative, a dichlorobenzene and a L-leucine derivative. | | Biological Activity | MLN-4760 is bioavailable and exhibits far greater selectivity for carboxypeptidase (IC50 = 0.44 nM against 50 pM human ACE2; [ZnCl2] = 10 μM, [MCA-APK(DNP)] = 50 μM) over bovine carboxypeptidase A or ACE peptidyldipeptidase activity (IC50 = 27 μM and >100 μM against 0.5 nM bovine CPDA and 1 nM porcine ACE, respectively; [Substrate] = 50 μM) and porcine ACE (IC50 = 27 and >100 μM, respectively). This reversible ACE2 inhibitor binds to the active site zinc with high-affinity and emulates the transition state during peptide hydrolysis. It reduces serum and kidney ACE 2 activity and abolishes angiotensin II-induced hypertension in mice. MLN-4760 selectively blocks angiotensin (ANG-(1-7)) formation in ACE2 wild type (WT) mice subjected to low ANG II concentrations (<0.1 μM), but at higher ANG II concentrations it does not affect ANG -(1-7) levels in mice. This ACE2 inhibitor enhances tumor necrosis factor (TNF) (10 pg/mL) stimulated expression of proinflammatory cytokines in murine endothelial cells, (1 μM using SVEC-40 line and primary aorta endothelial cultures) in vitro. MLN-4760 is widely employed for studying ACE2 involvement in kidney, cardiovascular and inflammatory bowel diseases via drinking water (10 mg/kg/d), i.v. (0.1 mg/kg), and s.c. (30 mg/kg/d to 300 mg/kg/12 h) injection in rats and mice, in vivo. The inhibitor leucine moiety is shown to simultaneously target ACE2 substrate S1 pocket with its isobutyl group and active site zinc via its carboxylate, while the compoundμs 3,5-dichlorobenzyl group effectively occupy S1μ subsite.
MLN-4760 also enables to study the effect of reduced ACE2 activity on the lung′s susceptibility for Coronavirus disease (COVID) related acute respiratory distress syndrome (ARDS). | | storage | Store at -20°C |
| | MLN-4760 Preparation Products And Raw materials |
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