Sigma-Aldrich Prcp Inhibitor

Assay

≥97% (HPLC)

Quality Level

100

Form

powder

Manufacturer/Tradename

Calbiochem^®

Storage Condition

OK to freeze

Color

white

Solubility

DMSO: 100 mg/mL

Storage Temp.

−20°C

General Description

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 micein vivo.A dichlorobenzimidazolopyrrolidinamide compound that acts as a highly potent PrCP-selective inhibitor (IC₅₀in 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.

Biochem/Physiol Actions

Cell permeable: yesPrimary Target
PrCPReversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Use only fresh DMSO for reconstitution.

Other Notes

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