5.04908

Myeloperoxidase Inhibitor-II

• Sinonimo/i: Myeloperoxidase Inhibitor-II, 4-(5-Fluoro-1H-indol-3-yl)butanamide, MPO Inhibitor II
• Formula empirica (notazione di Hill): C₁₂H₁₃FN₂O
• Numero CAS: 1256348-67-0
• Peso molecolare: 220.24
• Codice UNSPSC: 12352200

Proprietà

• Saggio: ≥95% (HPLC)
• Livello qualitativo: 100
• Forma fisica: powder
• Produttore/marchio commerciale: Calbiochem^®
• Condizioni di stoccaggio: OK to freeze; protect from light
• Colore: light beige
• Solubilità: DMSO: 100 mg/mL
• Temperatura di conservazione: 2-8°C

Descrizione

Descrizione generale

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.

A 5-fluorotryptamine derivative that inhibits myeloperoxidase/MPO activity (IC₅₀ = 18 nM) via direct affinity interaction with enzyme active site 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 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.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Azioni biochim/fisiol

Cell permeable: yes

Primary Target
myeloperoxidase

Reversible: yes

Confezionamento

Packaged under inert gas

Attenzione

Toxicity: Standard Handling (A)

Ricostituzione

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.

Altre note

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

Note legali

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

Informazioni sulla sicurezza

• Codice della classe di stoccaggio: 11 - Combustible Solids
• Classe di pericolosità dell'acqua (WGK): WGK 3
• Punto d’infiammabilità (°F): Not applicable
• Punto d’infiammabilità (°C): Not applicable