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MDL 28170

Catalog No.
A4412
Calpain and cathepsin B inhibitor, selective
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$60.00
In stock
10mg
$45.00
In stock
25mg
$100.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

MDL 28170 is a selective inhibitor, which inhibites calpain with Ki values of 10nM and cathepsin B with Ki values of 25 nM while does not inhibit trypsin-like serine proteases. And it can penetrate the blood–brain barrier rapidly and show the activity in inhibiting brain cysteine protease activity following systemic administration [1,2].

Calpain could affect reperfusion function directly through limited proteolysis of the sarcomeres.And function improvement of MDL-28170 during reperfusion were supported byexperimets. It is thought to act by blocking the sites of catalysis ofcalpains. The experiments also showed skinned muscle fibers which was isolated from the tropical of stunned ferret hearts reveal decreased sensitivity to Ca2+, and the decrease in sensitivity could be reversed if MDL-28170 is treated prior to ischemia and during early reperfusion [1].

When peritoneal mouse macrophages were pre-infected with trypomastigotes for 3 h , MDL28170 was able to reduce the viability of bloodstream trypomastigotes significantly with an IC50/24h value of 20.4 mM. Also, asparasitespre-treated with MDL28170 concentration rose from 6.25 to 50 mM, presenting a clear dose-dependent inhibition profile prior to of macrophage, where the corresponding inhibition from 20% increased to 50%. In addition, macrophages experimentally infected with T. cruzi which were treated with MDL 28170 presented a reduction in the percentage of infection even at the lowest concentrations of 6.25 mM [3].

Upon Ca2+ repletion in the isolated heart of rats, the hearts deteriorated immediately, revealing a marked depression in cardiac function and an enlarged myocardial injury area. This was accompanied by significant increases in lactate dehydrogenase, mitochondrial release of cytochrome c, the apoptotic index and degraded TnI. MDL 28170 significantly inhibited these changes, with the exception of TnI degradation [4].

References:
[1].  Urthaler F, Wolkowicz PE, Digerness SB, et al. MDL-28170, a membrane-permeantcalpain inhibitor, attenuates stunning and PKC epsilon proteolysis in reperfused ferret hearts. Cardiovasc Res, 1997, 35 (1): 60-7.
[2].  Li P, Wendy H, He Q, et al. Postischemic treatment withcalpain inhibitor MDL 28170ameliorates brain damage in a gerbil model of global ischemia, Neuroscience Letters, 1998, 247 :17–20.
[3].  V?′tor EV, Rubem F, Andre′ L, Effects of the calpain inhibitor MDL28170 on the clinically relevant forms of Trypanosomacruzi in vitro. J AntimicrobChemother , 2010, 65: 1395–1398.
[4].  Bi S H, Jin Z X, Zhang J Y, et al. Calpaininhibi tor MDL 28170 protectsagainst the Ca2+paradox in rat hearts.Clinical and Experimental Pharmacology and Physiology , 2012, 39:385–392 .

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt382.45
Cas No.88191-84-8
FormulaC22H26N2O4
Solubilityinsoluble in H2O; ≥16.75 mg/mL in DMSO; ≥25.05 mg/mL in EtOH with ultrasonic
Chemical Namebenzyl N-[(2S)-3-methyl-1-oxo-1-[(1-oxo-3-phenylpropan-2-yl)amino]butan-2-yl]carbamate
SDFDownload SDF
Canonical SMILESCC(C)C(C(=O)NC(CC1=CC=CC=C1)C=O)NC(=O)OCC2=CC=CC=C2
Shipping ConditionShip with blue ice, or upon other requests.
General tipsFor obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment:[1]

Cell lines

Schwann cells

Reaction Conditions

50 nM, 500 nM, 5 μM, or 50 μM MDL 28170 for 4 h incubation

Applications

MDL 28170 significantly enhanced Schwann cell survival in vitro in response to oxidative stress induced by application of H2O2, without reducing lactate dehydrogenase release.

Animal experiment:[2]

Animal models

A gerbil model of global ischemia

Dosage form

50 mg/kg

Injected at 0.5 and 3 h of recirculation following 5 min of global ischemia

Applications

The calpain inhibitor, MDL 28170, protected against cortical neuronal damage even if the treatment was delayed until 3 h after reperfusion. However, the neuroprotective effect of this agent was less pronounced in the hippocampal CA1 sector.

Note

The technical data provided above is for reference only.

References:

1. Hill CE, Guller Y, Raffa SJ, et al. A calpain inhibitor enhances the survival of Schwann cells in vitro and after transplantation into the injured spinal cord. Journal of Neurotrauma, 2010, 27(9): 1685-1695.

2. Li PA, Howlett W, He QP, et al. Postischemic treatment with calpain inhibitor MDL 28170 ameliorates brain damage in a gerbil model of global ischemia. Neuroscience Letters, 1998, 247(1): 17-20.

Biological Activity

Potent, selective inhibitor of calpain and cathepsin B (Ki values are 10 and 25 nM respectively) that does not inhibit trypsin-like serine proteases.
Targets calpain cathepsin B        
IC50 10nM 25nM        

Quality Control