Home Endocrinology & Hormones ACE inhibitor MLN-4760 For research use only.

MLN-4760

MLN-4760 (compound 16) is a potent and selective inhibitor of human angiotensin-converting enzyme 2 (ACE2) with IC50 of 0.44 nM. MLN-4760 also inhibits bovine carboxypeptidase A (CPDA) with IC50 of 27 μM.

MLN-4760 Chemical Structure

MLN-4760 Chemical Structure

CAS No. 305335-31-3

Purity & Quality Control

Batch: S894001 Water]86 mg/mL]false]Ethanol]10 mg/mL]false]DMSO]Insoluble]false Purity: 99.60%
99.60

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Biological Activity

Description MLN-4760 (compound 16) is a potent and selective inhibitor of human angiotensin-converting enzyme 2 (ACE2) with IC50 of 0.44 nM. MLN-4760 also inhibits bovine carboxypeptidase A (CPDA) with IC50 of 27 μM.
Targets
ACE2 [1]
(Cell-free assay)		 CPDA [1]
(Cell-free assay)
0.44 nM 27 μM
In vitro
In vitro

In vitro, conversion from angiotensin II to angiotensin-(1–7) by mouse ACE2 is blocked by MLN-4760 (10 μM). MLN-4760 inhibits both human and mouse ACE2 activity.[3] In huMNCs, MLN-4760-B (an isomer of MLN-4760) detects 63% ACE2 with 28-fold selectivity over ACE. In huCD34+ cells, MLN-4760-B detects 38% of ACE2 activity with 63-fold selectivity. In mu-heart and muMNCs, MLN-4760-B is 100- and 228-fold selective for ACE2, respectively. In muLin- cells, MLN-4760-B detects 25% ACE2 activity with a pIC50 of 6.3. The racemic mixture and MLN-4760-A shows lower efficacy and poor selectivity for ACE2 in MNCs and mu-heart.[4]
Cell Research Cell lines mononuclear cells (MNCs), huCD34+ cells, mu-lineage-depleted (muLin-) cells
Concentrations 0.01 nM to 300 μM
Incubation Time 1 h, 4 h
Method

In the case of cell lysates, 10 μg of total protein is assayed for activity in a buffer with the following composition: 50mM MES (4-morpholineethanesulphonic acid), 300mM NaCl, 10μM ZnCl2 and 0.01% Triton X-100, pH 6.5. Reaction is initiated by the addition of 5×10-5 M substrate. Where applicable, recombinant enzymes are used at a concentration of 0.01 μg per reaction. The fluorescence measurements are performed in the black microtiter plates in a total volume of 100 μl. The plates are read using a fluorescence plate reader SpectraMax M5 at an excitation wavelength 320 nm and emission wavelength 405 nm Fluorescence resulting from the substrate hydrolysis increased with time, and achieved maximum by 1 h with recombinant enzyme however with cell/tissue lysates the maximum fluorescence is observed by 4 h of incubation. Therefore fluorescence recorded at 1 and 4 h of reaction time is taken for calculation of percent enzyme inhibition, when using recombinant enzymes and cell/tissue lysates, respectively. ACE2 activity is defined as the ACE2 inhibitor-sensitive fluorescence and ACE activity is defined as the ACE inhibitor, captopril-sensitive fluorescence, and are expressed as percent inhibition. Unless specified, MLN4760 is used in concentration ranging from 0.01 nM to 300 μM.
In Vivo
In vivo

MLN-4760 blocks ACE2 activity, thus significantly reverses the elevation of carotid Ang-(1-7) level and the decline of carotid Ang II level induced by NaHS in mice. The anti-atherosclerotic property of NaHS is also significantly abolished by treatment with MLN-4760.[2]
Animal Research Animal Models C57BL/6J male apoE−/− mice
Dosages 0.5 mg/kg
Administration IP

Chemical Information & Solubility

Molecular Weight 428.31 Formula
C19H23Cl2N3O4
CAS No. 305335-31-3 SDF --
Smiles CC(C)CC(C(=O)O)NC(CC1=CN=CN1CC2=CC(=CC(=C2)Cl)Cl)C(=O)O
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

Water : 86 mg/mL

Ethanol : 10 mg/mL

DMSO : Insoluble ( Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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