5.04044

PrCP Inhibitor

• Synonyme(s) : PrCP Inhibitor, Angiotensinase C Inhibitor, Lysosomal Carboxypeptidase C Inhibitor, Lysosomal Pro-X Carboxypeptidase Inhibitor, PCP Inhibitor, Proline Carboxypeptidase Inhibitor, Prolylcarboxypeptidase Inhibitor, 2-Amino-N-((2 S,3 S)-3-(biphenyl-4-yl)-1-((, Angiotensinase C Inhibitor, Lysosomal Carboxypeptidase C Inhibitor, Lysosomal Pro-X Carboxypeptidase Inhibitor, PCP Inhibitor, Proline Carboxypeptidase Inhibitor, Prolylcarboxypeptidase Inhibitor, 2-Amino-N-((2S,3S)-3-(biphenyl-4-yl)-1-((2
• Formule empirique (notation de Hill): C₃₁H₃₃Cl₂N₅O₂
• Numéro CAS: 1252037-41-4
• Poids moléculaire : 578.53
• Code UNSPSC : 12352200
• Nomenclature NACRES : NA.77

Propriétés

• Pureté: ≥97% (HPLC)
• Niveau de qualité: 100
• Forme: powder
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze
• Couleur: white
• Solubilité: DMSO: 100 mg/mL
• Température de stockage: −20°C

Description

Description générale

A dichlorobenzimidazolopyrrolidinamide compound that acts as a highly potent PrCP-selective inhibitor (IC₅₀ = 1 nM against human PrCP; IC₅₀ = 2 and 8 nM against mouse PrCP, respectively, in the absence or presence of 1% mouse serum albumin), presumably via non-covalent catalytic site interaction, while exhibiting no significant potency toward panels of ion channels, receptors, and enzymes, including homologous serine proteases QPP, FAP, PEP, ACE2, DPP4, DPP8, and DPP9 (IC₅₀ >25 µM). Oral administration (100 mg/kg/d for 5 d) is reported to result in significant food intake reduction and body fat loss among high fat diet-induced obese mice in vivo.

A dichlorobenzimidazolopyrrolidinamide compound that acts as a highly potent PrCP-selective inhibitor (IC₅₀ in the absence/presence of 1% mouse serum albumin = 1 nM/1 nM and 2 nM/8 nM, respectively, against human and mouse PrCP-catalyzed Mca-APK(Dnp)-OH hydrolysis; Initial [Substrate] = 25 µM), presumably via non-covalent catalytic site interaction, while exhibiting no significant potency toward panels of ion channels, receptors, and enzymes, including homologous serine proteases QPP, FAP, PEP, ACE2, DPP4, DPP8, and DPP9 (IC₅₀ >25 µM). Despite its being a substrate of P-gp efflux transporters and ineffective CNS delivery across blood-brain barrier, peripheral PrCP inhibition via oral administration (100 mg/kg/d for 5 d; [Drug] = 380 nM and 50 nM, respectively, in blood and brain 24 h after last p.o. dosing) is reported to result in significant food intake reduction and body fat loss among high fat diet-induced obese mice (0.73 g fat reduction vs. 0,73 g fat gain in 5 d, respectively, with drug or vehicle treatment) in vivo. Drug treatment among PrCP^-/- obsese mice in comparison, results in only 1.1% weight loss primarily due to a decreased gain in muscle mass and little change in body fat.

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
PrCP

Reversible: yes

Conditionnement

Packaged under inert gas

Avertissement

Toxicity: Standard Handling (A)

Reconstitution

Use only fresh DMSO for reconstitution.

Autres remarques

Wu, Z., et al. 2012. Bioorg. Med. Chem. Lett.22, 1774.
Graham, T.H., et al. 2012. Bioorg. Med. Chem. Lett.22, 658.
Zhou, C., et al. 2010. J. Med. Chem.53, 7251.

Informations légales

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

Informations sur la sécurité

• Code de la classe de stockage: 11 - Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable