5.30613

IRAP Inhibitor, HFI-419

• Sinónimos: IRAP Inhibitor, HFI-419, (±)-Ethyl-2-acetamido-7-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate, HFI419, Insulin-Regulated Aminopeptidase Inhibitor
• Fórmula empírica (notación de Hill): C₁₉H₁₈N₂O₅
• Número de CAS: 1110650-72-0
• Peso molecular: 354.36
• Código UNSPSC: 12352200
• ID de la sustancia en PubChem: 42601512

Propiedades

• Análisis: ≥97% (HPLC)
• Nivel de calidad: 100
• formulario: powder
• fabricante / nombre comercial: Calbiochem^®
• condiciones de almacenamiento: OK to freeze; protect from light
• color: off-white
• solubilidad: DMSO: 100 mg/mL
• temp. de almacenamiento: 2-8°C
• cadena SMILES: CCOC(=O)C1=C(OC2=C(C1C3=CN=CC=C3)C=CC(=C2)O)NC(=O)C

Descripción

Descripción general

The racemic mixture of an aqueous soluble (at least 50 µg/mL or 140 µM at pH 6.5) pyridinyl-4H-benzopyran compound that inhibits insulin-regulated (IRAP) aminopeptidase activity by competing against substrate for IRAP extracellular catalytic site binding (K_i = 0.48 µM; using 25 µM Leu-AMC as substrate) with concomitant interaction with active site zinc via its acetamide, while displaying little potency against glucose-6-phosphatase, aminopeptidase N, ACE1, leukotriene A4 hydrolase, or ER-associated aminopeptidases 1 & 2 (≤13% inhibition at 100 µM). Reported to boost 1 mM dibutyryl cAMP-evoked glucose uptake in cultured rat hippocampal slices (68% higher uptake in 5 min than dbcAMP alone without 100 nM HFI-419) in vitro and exhibit in vivo memory-enhancing efficacay in an object recognition test when administered directly into the cerebral lateral ventricle of rats via a cannula implant (0.1 or 1.0 nmol/2 µL/rat). HFI-419 is reported to hydrolyze into slightly less potent HFI-142 (K_i = 2.0 µM) after i.v. (plasma t_1/2 = 11 min; 2 mg/kg) or i.p (plasma t_1/2 = 4.6 h; 10 mg/kg) injection in rats, although HFI-142 is more stable and likely exhibits better blood-brain permeability (Blood:Brain HFI-142 ratio = 3.36 and 0.38, respectively, 0.5 and 4 h post single 3 mg HFI-419/kg i.v. injection).

The racemic mixture of an aqueous soluble pyridinyl-4H-benzopyran compound that inhibits insulin-regulated aminopeptidase (IRAP) activity by competing against substrate for IRAP extracellular catalytic site binding (K_i = 0.48 µM against 25 µM Leu-AMC), while displaying little potency against glucose-6-phosphatase, aminopeptidae N, ACE1, leukotriene A4 hydrolase, or ER-associated aminopeptidases 1 & 2. Reported to boost 1 mM dibutyryl cAMP-evoked glucose uptake in cultured rat hippocampal slices (68% higher uptake with 100 nM HFI-419 than dbcAMP alone) in vitro and exhibit in vivo memory-enhancing efficacay in an object recognition test via direct cerebral lateral ventricle administration (0.1 or 1.0 nmol/2 µL/rat). HFI-419 is reported to hydrolyze into the less potent HFI-142 (K_i = 2.0 µM) after i.v. or i.p. injection in rats, although HFI-142 is more stable and likely exhibits better blood-brain permeability.

Acciones bioquímicas o fisiológicas

Cell permeable: yes

Primary Target
IRAP

Reversible: yes

Envase

Packaged under inert gas

Advertencia

Toxicity: Standard Handling (A)

Reconstitución

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Use only fresh DMSO for reconstitution.

Otras notas

Mountford, S.J., et al. 2014. J. Med. Chem.57, 1368.
Albiston, A.L., et al. 2011. Br. J. Pharmacol.164, 37.
Albiston, A.L., et al. 2010. Mol. Pharmacol.78, 600.
Albiston, A.L., et al. 2008. FASEB J.22, 4209.

Información legal

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

Información de seguridad

• Código de clase de almacenamiento: 11 - Combustible Solids
• Clase de riesgo para el agua (WGK): WGK 3
• Punto de inflamabilidad (°F): Not applicable
• Punto de inflamabilidad (°C): Not applicable