We have previously shown that cinnamoyl derivatives of 14β-amino-17-cyclopropylmethyl-7,8-dihydronormorphinone and 7α-aminomethyl-6,14-endoethanonororipavine have pronounced pseudoirreversible μ opioid receptor (MOR) antagonism. The present communication describes the synthesis and evaluation of fumaroylamino analogues of these cinnamoylamino derivatives together with some related fumaroyl deri...

Obesity is a significant risk factor for certain cancers, including hepatocellular carcinoma (HCC). Leptin, a hormone secreted by white adipose tissue, precipitates HCC development. Epidemiology data show that men have a much higher incidence of HCC than women, suggesting that estrogens and its receptors may inhibit HCC development and progression. Whether estrogens antagonize oncogenic action ...

Cation-π interactions have been demonstrated to play a major role in agonist-binding in Cys-loop receptors. However, neither the aromatic amino acid contributing to this interaction nor its location is conserved among Cys-loop receptors. Likewise, it is not clear how many different agonists of a given receptor form a cation-π interaction or, if they do, whether it is with the same aromatic amin...

The biased agonism of the G protein-coupled receptors (GPCRs), where in addition to a traditional G protein-signaling pathway a GPCR promotes intracellular signals though β-arrestin, is a novel paradigm in pharmacology. Biochemical and biophysical studies have suggested that a GPCR forms a distinct ensemble of conformations signaling through the G protein and β-arrestin. Here we report on the d...

BACKGROUND Activating G-protein coupled receptor 119 (GPR119) by its agonists can stimulate glucagon like peptide-1 (GLP-1) release. GLP-1 is rapidly degraded and inactivated by dipeptidylpeptidase-IV (DPP-IV). We studied the efficiency of combining PSN632408, a GPR119 agonist, with sitagliptin, a DPP-IV inhibitor, on β-cell regeneration in diabetic mice. MATERIALS & METHODS Diabetes in C57BL...

β-Adrenergic receptor (βAR) agonists reduce body fat in mammals and birds. Synthetic lipid metabolism is decreased in βAR agonist-treated animals or in agonist-treated adipocytes in vitro. Degradative lipid metabolism is increased by βAR agonists in adipocytes in vitro and in vivo. The βAR agonist effects are blocked by βAR antagonists. In mammalian tissues, there are at least three distinct βA...

Zilpaterol hydrochloride is a β-adrenergic agonist, which belongs to a group of compounds known as catecholamines. β-Adrenergic agonists activate β-receptors in muscle and fat causing increased lipolysis, decreased lipogenesis or increased protein accretion (Mersmann, 1998), or both. β-Adrenergic agonists vary greatly in their effect on meat animals. Supplementation of diets with β-agonists can...

Fatty acids activate GPR40 and K+ channels to modulate β-cell function. Herein, we describe the design and synthesis of FAAzo-10, a light-controllable GPR40 agonist based on Gw-9508. FAAzo-10 is a potent GPR40 agonist in the trans-configuration and can be inactivated on isomerization to cis with UV-A light. Irradiation with blue light reverses this effect, allowing FAAzo-10 activity to be cycle...

Opiates produce analgesia via G-protein signaling, and adverse effects, such as respiratory depression decreased bowel motility, by β-arrestin pathway. Oliceridine, a G protein-biased MOR agonist, only presents modest safety advantages compared to other opiates in clinical trials, possibly due its limited bias. Our previous study shown that LPM3480392, full biased is selective for the Gi pathwa...