jm7b00805_si_001.csv (2.94 kB)
Polypharmacology of N6‑(3-Iodobenzyl)adenosine-5′‑N‑methyluronamide (IB-MECA) and Related A3 Adenosine Receptor Ligands: Peroxisome Proliferator Activated Receptor (PPAR) γ Partial Agonist and PPARδ Antagonist Activity Suggests Their Antidiabetic Potential
dataset
posted on 2017-08-11, 00:00 authored by Jinha Yu, Seyeon Ahn, Hee Jin Kim, Moonyoung Lee, Sungjin Ahn, Jungmin Kim, Sun Hee Jin, Eunyoung Lee, Gyudong Kim, Jae Hoon Cheong, Kenneth A. Jacobson, Lak Shin Jeong, Minsoo NohA3 adenosine receptor
(AR) ligands including A3 AR agonist, N6-(3-iodobenzyl)adenosine-5′-N-methyluronamide (1a, IB-MECA) were
examined for adiponectin production in human bone marrow mesenchymal
stem cells (hBM-MSCs). In this model, 1a significantly
increased adiponectin production, which is associated with improved
insulin sensitivity. However, A3 AR antagonists also promoted
adiponectin production in hBM-MSCs, indicating that the A3 AR pathway may not be directly involved in the adiponectin promoting
activity. In a target deconvolution study, their adiponectin-promoting
activity was significantly correlated to their binding activity to
both peroxisome proliferator activated receptor (PPAR) γ and
PPARδ. They functioned as both PPARγ partial agonists
and PPARδ antagonists. In the diabetic mouse model, 1a and its structural analogues A3 AR antagonists significantly
decreased the serum levels of glucose and triglyceride, supporting
their antidiabetic potential. These findings indicate that the polypharmacophore
of these compounds may provide therapeutic insight into their multipotent
efficacy against various human diseases.