5.04908

Myeloperoxidase Inhibitor-II

• Synonyma: Myeloperoxidase Inhibitor-II, 4-(5-Fluoro-1H-indol-3-yl)butanamide, MPO Inhibitor II
• Empirický vzorec (Hillův zápis): C₁₂H₁₃FN₂O
• Číslo CAS: 1256348-67-0
• Molekulová hmotnost: 220.24
• MDL number: MFCD25957182
• NACRES: NA.77
• UNSPSC Code: 12352200
• Assay: ≥95% (HPLC)
• Form: powder
• Storage condition: OK to freeze, protect from light

Vlastnosti

• assay: ≥95% (HPLC)
• Quality Segment: 100
• 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

Popis

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 (K_i = 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)

Bezpečnostní informace

• Skladovací třída: 11 - Combustible Solids
• wgk: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable