Basic information Safety Supplier Related

MLN-4760

Basic information Safety Supplier Related

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
Mol File:
305335-31-3.mol
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MLN-4760 Chemical Properties

storage temp. 
Store at -20°C
solubility 
DMSO: soluble
form 
A solid
color 
Off-white to light yellow
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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-4760Supplier

Shanghai Luofa Biochemical Technology Co., Ltd. Gold
Tel
021-51111890 15317326293
Email
sales@molnova.com
ShangHai Caerulum Pharma Discovery Co., Ltd.
Tel
18149758185 18149758185
Email
sales-cpd@caerulumpharma.com
ChemStrong Scientific Co.,Ltd
Tel
0755-0755-66853366 13670046396
Email
sales@chem-strong.com
Shanghai Lollane Biological Technology Co.,Ltd.
Tel
021-52996696,15000506266 15000506266
Shanghai EFE Biological Technology Co., Ltd.
Tel
021-65675885 18964387627
Email
info@efebio.com
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MLN-4760(305335-31-3)Related Product Information