Binding and functional affinity of some newly synthesized phenethylamine and phenoxypropanolamine derivatives for their agonistic activity at recombinant human β3‐adrenoceptor

  title={Binding and functional affinity of some newly synthesized phenethylamine and phenoxypropanolamine derivatives for their agonistic activity at recombinant human $\beta$3‐adrenoceptor},
  author={Maruf Ahmed and Yoko Hanaoka and Takafumi Nagatomo and Tatsuya Kiso and Takao Kakita and Hitoshi Kurose and Takuya Nagao},
  journal={Journal of Pharmacy and Pharmacology},
β3‐Adrenoceptor is the predominant β‐adrenoceptor in adipocytes and has drawn much attention during the investigation for anti‐obesity and antidiabetes therapeutics. Thirteen new compounds have been evaluated for their potencies and efficacies as β3‐adrenoceptor agonists on human β3‐ adrenoceptor expressed in COS‐7 and Chinese hamster ovary (CHO) cells using radio ligand binding assay and cyclic AMP (cAMP) accumulation assay. Phenoxypropanolamine derivatives, SWR‐0334NA (([E)‐[4‐[5‐[(3‐phenoxy… Expand
Comparison of the binding affinity of some newly synthesized phenylethanolamine and phenoxypropanolamine compounds at recombinant human β‐ and α1‐adrenoceptor subtypes
Six new compounds were evaluated and the binding affinities for human α1‐adrenoceptors expressed in Chinese hamster ovary (CHO) cells were compared using a radioligand‐binding assay to confirm the finding of this manuscript that this phenoxypropanolamine group of β2‐phenyl‐2‐hydroxyethyl ligands could also be used as α1-adrenOceptor ligands. Expand
Zur Funktion des β3-Adrenozeptors am Herzen: Signaltransduktion, inotroper Effekt und therapeutischer Ausblick
The β3-adrenoceptor is discussed as a possible target for the pharmacological therapy of heart failure and may have a protective effect against excessive chatecolaminergic stimulation as it occurs during somatic and mental stress and during heart failure. Expand


Mediation of most atypical effects by species homologues of the β3‐adrenoceptor
Compounds active on atypical β‐sites of other tissues such as heart and digestive tract were also potent on the β3‐adrenoceptor expressed in Chinese hamster ovary cells, suggesting that this receptor mediates most of the atypicals properties described in various tissues, and that differences in ligand effects may result from tissue‐related specificities. Expand
Anti-obesity and anti-diabetic activities of a new beta3 adrenergic receptor agonist, (S)-(Z)-[4-[[1-[2-[(2-hydroxy-3-phenoxypropyl)]amino]ethyl]-1-propenyl] phenoxy] acetic acid ethanedioic acid (SWR-0342SA), in KK-Ay mice.
The results indicated that SWR-0342SA is a selective beta3-AR agonist, and possesses potent anti-di diabetic activity, and that the anti-obesity activity is inferior to theAnti-diabetic activity. Expand
Biochemical and functional characterization of 1-benzyl substituted trimetoquinol affinity analogs on rat and human β-adrenoceptors
The lipophilic 1-benzyl ring of TMQ analogs interacts with a hydrophobic region of the β-AR that may represent an exo-site or an allosteric binding site of trimetoquinol with β-adrenoceptors, and demonstrates significant concentration-dependent irreversible binding to the rat β 3 -AR. Expand
Molecular characterization of the mouse beta 3‐adrenergic receptor: relationship with the atypical receptor of adipocytes.
Northern blot analyses indicate that the Beta 3AR gene is mainly expressed in mouse brown and white adipose tissues, suggesting that the murine beta 3AR described here is the atypical beta AR involved in the control of energy expenditure in fat tissue. Expand
Agonist potency at the cloned human beta-3 adrenoceptor depends on receptor expression level and nature of assay.
The cloned human beta-3 adrenoceptor was expressed in Chinese hamster ovary cells at three different levels (130, 400 and 3000 fmol/mg). The potency and intrinsic activity of a range of agonists inExpand
Atypical β-adrenoceptor on brown adipocytes as target for anti-obesity drugs
A novel group of β-adrenoceptor agonists that selectively stimulate lipolysis in brown adipocytes are found and this has been demonstrated with BRL 26830A, BRL 33725A and BRL 35135A. Expand
Molecular characterization of pharmacological properties of T-0509 for beta-adrenoceptors.
The results indicate that T-0509 is a relatively specific beta 1-adrenoceptor agonist with a high intrinsic activity as compared with isoproterenol. Expand
Molecular characterization of the human beta 3-adrenergic receptor.
Novel beta-AR agonists having high thermogenic, antiobesity, and antidiabetic activities in animal models are among the most potent stimulators of the beta 3-AR. Expand
Mitigation of obesity by BRL 26830A, a new beta-adrenoceptor agonist, in MSG obese mice.
It is suggested that BRL 26830A, which is a new beta-adrenoceptor agonist, stimulates BAT thermogenesis, increases RMR, and reduces WAT, thus contributing to the mitigation of obesity. Expand
A mutation-induced activated state of the beta 2-adrenergic receptor. Extending the ternary complex model.
The experimental findings with the mutant receptor cannot be adequately rationalized within the theoretical framework of the Ternary Complex Model, and an extended version of this model that includes an explicit isomerization of the receptor to an active state closely models all the findings for both the mutant and the wild-type receptors. Expand