5.30613

IRAP Inhibitor, HFI-419

• Synonym(s): IRAP Inhibitor, HFI-419, (±)-Ethyl-2-acetamido-7-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate, HFI419, Insulin-Regulated Aminopeptidase Inhibitor
• Empirical Formula (Hill Notation): C₁₉H₁₈N₂O₅
• CAS Number: 1110650-72-0
• Molecular Weight: 354.36
• MDL number: MFCD32671930
• UNSPSC Code: 12352200
• NACRES: NA.77
• PubChem Substance ID: 42601512
• Assay: ≥97% (HPLC)
• Form: powder
• Storage condition: OK to freeze, protect from light

Properties

• assay: ≥97% (HPLC)
• Quality Segment: 100
• form: powder
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze, protect from light
• color: off-white
• solubility: DMSO: 100 mg/mL
• storage temp.: 2-8°C
• SMILES string: CCOC(=O)C1=C(OC2=C(C1C3=CN=CC=C3)C=CC(=C2)O)NC(=O)C
• InChI: 1S/C19H18N2O5/c1-3-25-19(24)17-16(12-5-4-8-20-10-12)14-7-6-13(23)9-15(14)26-18(17)21-11(2)22/h4-10,16,23H,3H2,1-2H3,(H,21,22)
• InChI key: GGBHINRNYAAYMX-UHFFFAOYSA-N

Description

General description

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).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
IRAP

Reversible: yes

Packaging

Packaged under inert gas

Preparation Note

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.

Other Notes

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.

Legal Information

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

Disclaimer

Toxicity: Standard Handling (A)

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable