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Merck

5.04908

Sigma-Aldrich

Myeloperoxidase Inhibitor-II

Synonym(s):

Myeloperoxidase Inhibitor-II, 4-(5-Fluoro-1H-indol-3-yl)butanamide, MPO Inhibitor II

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About This Item

Empirical Formula (Hill Notation):
C12H13FN2O
CAS Number:
Molecular Weight:
220.24
MDL number:
UNSPSC Code:
12352200
NACRES:
NA.77

Assay

≥95% (HPLC)

Quality Level

form

powder

manufacturer/tradename

Calbiochem®

storage condition

OK to freeze
protect from light

color

light beige

solubility

DMSO: 100 mg/mL

storage temp.

2-8°C

General description

A 5-fluorotryptamine derivative that inhibitis the MPO-catalyzed Cl-/chloride-to-OCl-/hypochlorite oxidation in the presence of H2O2 (IC50 = 18 nM by taurine/2-aminoethan-sulfonic acid chlorination assay) as well as MPO-mediated LDL ApoB-100 (ApoB100; apolipoprotein B-100) oxidation (IC50 = 18 nM by ELISA) via direct affinity binding at the myeloperoxidase active site through ϖ-ϖ interaction between its indole and the the enzyme′s heme pyrrole ring D, while exhibiting much reduced affinity toward serotonin reuptake transporter/SERT (Ki = 631 nM). Kinetic studies reveal that the inhibitor acts as a good one-electron donor for the intermediate Compound I "Fe(IV)=O...Por•+", facilitating the formation (k3 = 1,6 x 107 M-1 s-1) of Compound II (Fe(IV)-OH...Por) and thereby preventing the reduction of Compound I directly to the resting state "Fe(IV)...Por" via the "halogenation cycle", while, on the other hand, behaves as a poor electron donor for Compound II, thereby preventing the completion of the "peroxidase cycle" by stalling the further reduction of Compound II to the resting state (k4 = 92 M-1 s-1). Toxicology study using Wistar Han male rats reports no signs of adverse effects post single 10 mg/kg i.p. dosage, while signs of adverse effects are observed within the 24 h, but not after, post a higher i.p. dosage at 100 mg/kg.

Biochem/physiol Actions

Cell permeable: yes
Primary Target
myeloperoxidase
Reversible: yes

Packaging

Packaged under inert gas

Preparation Note

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

Other Notes

Soubhye, J., et al. 2013. J. Med. Chem.56, 3943.
Soubhye, J., et al. 2010. J. Med. Chem.53, 8747.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Disclaimer

Toxicity: Standard Handling (A)

Storage Class Code

11 - Combustible Solids

WGK

WGK 3

Flash Point(F)

Not applicable

Flash Point(C)

Not applicable


Certificates of Analysis (COA)

Search for Certificates of Analysis (COA) by entering the products Lot/Batch Number. Lot and Batch Numbers can be found on a product’s label following the words ‘Lot’ or ‘Batch’.

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