Adrenergic receptors (also known as adrenoceptors, ARs) belong to the guanine nucleotide-binding G protein-coupled receptor (GPCR) superfamily. And Adrenergic receptors are membrane receptors that activate heterotrimeric G proteins following the binding of a ligand. Besides, adrenergic receptors are the targets of catecholamines, especially norepinephrine and epinephrine. Here, there are two main groups of adrenergic receptors, α (α1 and α2) and β (β1, β2 and β3). Henceforth, the response to GPCR stimulus can be modified by various conditions, including chronic stimulation, acidosis, cell hypoxia, and aging.
So far, the beta-3 adrenergic receptor (β3-AR) is the least studied isotype of the beta-adrenergic sub-family. And the β3-AR is exists in several tissues revealing. Recently, β3-AR has become an appealing target for novel pharmacological approaches in several areas: including metabolic, cardiovascular, urinary, and ocular disease. Importantly, β3-AR agonist Mirabegron is the first of this class of compounds that has been approved for the treatment of overactive bladder syndrome and one of the few alternatives to anticholinergic medications. Today, we will introduce a potent, highly selective a potent β3-adrenergic receptor antagonist, L748337.
L748337 is a potent and competitive β3-adrenergic receptor antagonist. Importantly, L748337 displays selectivity over β1 and β2 receptors. L748337 has potent anti-tumor activity. Moreover, L748337 is one of the most popular antagonist of β3-AR. Importantly, L748337 is currently one of the very few antagonists with good selectivity for human β3-AR on the market. Meanwhile, L748337 inhibits iNOS expression, attenuates nitric oxide-induced cell proliferation and induces apoptosis in in vitro. What’s more, it decreases the growth of melanoma in vivo. By the way, L748337 also can couple with Gi to activate MAPK signaling.
All in all, L748337 is a potent, selective and competitive antagonist of β3-adrenergic receptor.
 Schena G, et, al. Cells. 2019 Apr 16;8(4):357.