BIIE-0246 hydrochloride

BIIE-0246 hydrochloride (AR-H 053591 hydrochloride) is a potent and selective NPY2R ( neuropeptide Y receptor 2) antagonist with an IC₅₀ value of 15 nM for rat [ 125 I]PYY 3-36. BIIE-0246 hydrochloride decreases the expression of p-AKT S473, P-p44/42 MAPK under the NPY-stimulated. BIIE-0246 hydrochloride reduces albuminuria in ADR nephropathy ^{[1] [2] [3]}.

In Vivo, BIIE-0246 hydrochloride (1.3 mg/kg; I.p.; daily for 2 or 4.5 weeks) prevents diet-induced obesity in OE-NPYDβH mice, but enhances obesity in WT Mice^[1]. BIIE-0246 hydrochloride (10 µg/day; i.p.; daily for 14 days) reduces albuminuria in ADR (adriamycin) nephropathy^[3].

In Vitro, BIIE-0246 hydrochloride (1 µM; 24 h) decreases the expression of p-AKT S473, P-p44/42 MAPK under the NPY-stimulated (10, 100 ng/mL) in mouse podocytes^[3].

References:
[1]. Ailanen L, et al. Peripherally Administered Y2-Receptor Antagonist BIIE0246 Prevents Diet-Induced Obesity in Mice With Excess Neuropeptide Y, but Enhances Obesity in Control Mice. Front Pharmacol. 2018 Apr 5;9:319.
[2]. Dumont Y, et al. BIIE0246, a potent and highly selective non-peptide neuropeptide Y Y(2) receptor antagonist. Br J Pharmacol. 2000 Mar;129(6):1075-88.
[3]. Lay AC, et al. A role for NPY-NPY2R signaling in albuminuric kidney disease. Proc Natl Acad Sci U S A. 2020 Jul 7;117(27):15862-15873.