AdipoRon is a selective, orally active adiponectin receptor (AdipoR) agonist with Kd values of 1.8μM and 3.1μM for AdipoR1 and AdipoR2, respectively[1]. AdipoRon has potential therapeutic effects in a variety of metabolic, cardiovascular and neurological diseases [2].
In vitro, AdipoRon (5-50μM) pretreated L02 cells attenuated the expression of TNF-α and TGF-β1 in a dose-dependent manner without cytotoxicity[3]. AdipoRon (20μg/mL) treated Saos-2 and U2OS osteosarcoma cells, significantly inhibited cell proliferation, and induced G0/G1 phase aggregation and S phase reduction[4]. AdipoRon (25μM) treated human luteinized granulosa cells, inhibited cell proliferation, increased phosphodiesterase activity, promoted cyclic adenosine monophosphate (cAMP) production and decreased estrogen secretion [5].
In vivo, AdipoRon (0.1 and 0.5 mg/kg) treatment in D-GalN-induced acute liver injury mice restored hepatic lesions, reduced pro-inflammatory macrophage infiltration, and decreased the expression of TNF-α, TGF-β1, IL-1β, and IL-6, while also promoting the activation of AMPK through phosphorylation[3]. AdipoRon (50 mg/kg) can significantly improve cardiac function and reduce post-ischemic cardiomyocyte apoptosis in mice treated with myocardial ischemia/reperfusion (MI/R) injury through oral administration [6].
References:
[1] Okada-Iwabu M, Yamauchi T, Iwabu M, et al. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity[J]. Nature, 2013, 503(7477): 493-499.
[2] Bhat I A, Kabeer S W, Reza M I, et al. AdipoRon: a novel insulin sensitizer in various complications and the underlying mechanisms: a review[J]. Current Molecular Pharmacology, 2020, 13(2): 94-107.
[3] Wang Y, Yu W, et al. Hepatoprotective effects of AdipoRon against d-galactosamine-induced liver injury in mice[J]. European Journal of Pharmaceutical Sciences, 2016.
[4] Sapio L, Nigro E, Ragone A, et al. AdipoRon affects cell cycle progression and inhibits proliferation in human osteosarcoma cells[J]. Journal of Oncology, 2020.
[5] Grandhaye J, Hmadeh S, Plotton I, et al. The adiponectin agonist, AdipoRon, inhibits steroidogenesis and cell proliferation in human luteinized granulosa cells[J]. Molecular and cellular endocrinology, 2021, 520: 111080.
[6] Zhang Y, Zhao J, Li R, et al. AdipoRon, the first orally active adiponectin receptor activator, attenuates postischemic myocardial apoptosis through both AMPK-mediated and AMPK-independent signalings[J]. American Journal of Physiology-Endocrinology and Metabolism, 2015, 309(3): E275-E282.
AdipoRon是一种选择性、具有口服活性的脂联素受体（AdipoR）激动剂，对AdipoR1和AdipoR2的Kd值分别为1.8μM和3.1μM[1]。AdipoRon在多种代谢、心血管和神经系统疾病中具有潜在治疗作用[2]。
在体外，AdipoRon（5-50μM）预处理L02细胞，以剂量依赖性方式减弱TNF-α和TGF-β1的表达，且无细胞毒性[3]。AdipoRon（20μg/mL）处理Saos-2和U2OS 骨肉瘤细胞，显著抑制了细胞增殖，并诱导G0/G1期聚集和S期减少[4]。AdipoRon（25μM）处理人类黄素化颗粒细胞，抑制了细胞增殖，提高了磷酸二酯酶活性，促进了环磷酸腺苷（cAMP）产生和雌激素分泌下降[5]。
在体内，AdipoRon（0.1和0.5mg/kg）治疗D-GalN诱导的急性肝损伤小鼠，恢复了肝病变，减少促炎巨噬细胞浸润，减少TNF-α、TGF-β1、白细IL-1β和IL-6的表达，同时通过磷酸化促进AMPK的激活[3]。AdipoRon（50mg/kg）通过口服治疗心肌缺血/再灌注（MI/R）损伤小鼠，显著改善心功能，减少缺血后心肌细胞凋亡[6]。