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5.30616 Sigma-Aldrich

ACE2 Inhibitor, MLN-4760 - CAS 305335-31-3 - Calbiochem

Synonym: ( S, S)-2-(1-Carboxy-2-(3-(3,5-dichlorobenzyl)-3H-imidazol-4-yl)-ethylamino)-4-methylpentanoic acid, 2( S)-(1( S)-Carboxy-2-(3-(3,5-dichlorobenzyl)-3H-imidazol-4-yl)-ethylamino)-4-methylpentanoic acid, Angiotensin-Converting E, (S,S)-2-(1-Carboxy-2-(3-(3,5-dichlorobenzyl)-3H-imidazol-4-yl)-ethylamino)-4-methylpentanoic acid, 2(S)-(1(S)-Carboxy-2-(3-(3,5-dichlorobenzyl)-3H-imidazol-4-yl)-ethylamino)-4-methylpentanoic acid, Angiotensin-Converting Enzyme, ACE2 Inhibitor, MLN-4760 - CAS 305335-31-3 - Calbiochem

  • CAS Number 305335-31-3

  • Empirical Formula (Hill Notation) C19H23Cl2N3O4

  • Molecular Weight 428.31

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Properties

assay   ≥97% (HPLC)
form   powder
mfr. no.   Calbiochem®
storage condition   OK to freeze
  protect from light
storage conditions   +2C to +8C
color   white
solubility   DMSO: 100 mg/mL

Description

General description

A cell-permeable, bioavailable, highly potent, inhibitor of angiotensin converting enzyme 2 (ACE2; IC50 = 440 pM against soluble human ACE2) that exhibits far greater selectivity over bovine bovine carboxypeptidase A and porcine ACE (IC50 = 27 and >100 µM, respectively). Binds to the active site zinc with high-affinity and emulates the transition state during peptide hydrolysis. Reduces serum and kidney ACE 2 activity and abolishes angiotensin II-induced hypertension in mice. Shown to selectively block ANG-(1-7) formation in ACE2 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.

A selective and highly potent inhibitor against ACE2 carboxypeptidase activity (IC50 = 0.44 nM against 50 pM human ACE2; [ZnCl2] = 10 µM, [MCA-APK(DNP)] = 50 µM) with little potency toward 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). Enhances 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 and 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 compound′s 3,5-dichlorobenzyl group effectively occupy S1′ subsite.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
soluble human ACE2

Reversible: yes

Target IC50: 440 pM for soluble human ACE2

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Tikellis, C., et al. 2014. Am. J. Physiol. Renal Physiol.306, F773.
Grobe, N., et al. 2013. Am. J. Physiol. Cell Physiol 304, C945.
Ye, M., et al. 2012. Hypertension60, 730.
Dilauro, M., et al. 2010. Am. J. Physiol. Renal Physiol.298, F1523.
Thomas, M.C., et al. 2010. Circ. Res.107, 888.
Trask, A.J., et al. 2010. Am. J. Hypertens.23, 687.
Byrnes, J.J., et al. 2009. Inflamm. Res.58, 819.
Soler, M.J., et al. 2007. Kidney Int.72, 614.
Towler, P., et al. 2004. J. Biol. Chem.279, 17996.
Dales, N.A., et al. 2002. J. Am. Chem. Soc.124, 11852.

Safety & Documentation

Safety Information

Safety Information for this product is unavailable at this time.

Documents

Certificate of Analysis (COA)

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Protocols & Articles

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Peer-Reviewed Papers
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References

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