Delving into the Latest Updates on AdipoRon with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

ADIPOR1 x ADIPOR2

Action

agonists

Mechanism

ADIPOR1 agonists(Adiponectin receptor protein 1 agonists), ADIPOR2 agonists(Adiponectin receptor protein 2 agonists)

Therapeutic Areas

NeoplasmsCardiovascular DiseasesEndocrinology and Metabolic Disease+ [2]

Active Indication

Diminished ovarian reserveBreast CancerDiabetic Cardiomyopathies+ [3]

Inactive Indication-

Originator Organization

University of Tokyo

Active Organization

The Catholic University of KoreaNational Taiwan University College of Medicine

Guangzhou Medical University

+ [1]

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC27H28N2O3

InChIKeySHHUPGSHGSNPDB-UHFFFAOYSA-N

CAS Registry924416-43-3

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, for which effective therapeutic strategies remain limited. AdipoRon, a synthetic adiponectin receptor agonist, has been reported to possess anti-inflammatory properties. In this study, we evaluated the therapeutic potential and underlying mechanisms of AdipoRon in alleviating RA-related synovial inflammatory lesions. In an adjuvant-induced arthritis (AIA) rat model, AdipoRon treatment markedly improved clinical scores and reduced ankle swelling. Histological and micro-CT evaluations demonstrated AdipoRon alleviated synovial inflammatory lesions, cartilage degradation, and bone erosion. In vitro, AdipoRon dose-dependently suppressed TNF-α-induced proliferation, migration, and invasion of fibroblast-like synoviocytes (FLSs). RNA sequencing identified Keratin 7 (Krt7) as a key gene responsive to AdipoRon. Immunofluorescence analysis confirmed upregulated Krt7 expression in RA patient samples. Functional studies demonstrated that Krt7 overexpression promoted synovial inflammation and FLSs migration and invasion, whereas AdipoRon alleviated these pathological processes by downregulating Krt7. Collectively, these results demonstrate that AdipoRon ameliorates synovial inflammation and abnormal FLSs activation by modulating Krt7, therefore supporting its further development as a therapeutic candidate for RA.

01 Aug 2026·GUT

A20-mediated KEAP1 ubiquitination orchestrates hepatocyte ferroptosis to ameliorate autoimmune hepatitis

Article

Author: Ye, Zhenghao ; Li, Wanneng ; Liu, Mei ; Wang, Lijia ; Lin, Zhuoying ; Yu, Meiping ; Wang, Shuhui ; Tian, Dean ; Wang, Han ; Xu, Jiaxin ; Yan, Xinmei ; Chen, Yu ; Lei, Yu ; Han, Ping ; Yan, Wei ; Xiao, Fang

Background:

Autoimmune hepatitis (AIH) is characterised by death of hepatocytes and chronic inflammation. Patients with deleterious variants in A20 are identified with AIH presentations and immune activation. However, it remains unclear how A20 dysregulation contributes to AIH pathogenesis.

Objective:

This study elucidates the role and mechanism of A20 in AIH progression and its therapeutic potential.

Design:

A20 expression was analysed in patient sample and AIH mouse model. A20 function was explored in mice with hepatocyte-specific A20 knockout and overactivation and wild type controls. Liver samples were assessed by histology, immunoblot and electron microscopy. Proteomics, mass spectrometry, co-immunoprecipitation and site‐specific mutation experiments were used to elucidate underlying mechanisms. AdipoRon was used to identify the effects of pharmacological induction of A20 on AIH.

Results:

A20 expression is reduced in livers of individuals with AIH. In experimental AIH, hepatocyte-specific A20 depletion aggravates hepatic inflammation and fibrosis, enhances ferroptosis of hepatocytes and increases sensitivity to ferroptosis inhibitors, while A20 overexpression ameliorates AIH pathology and reduces hepatocyte ferroptosis. Mechanistically, A20 is found to interact with KEAP1 and mediate its K48-linked polyubiquitination degradation, promoting NRF2 accumulation and nuclear translocation to enhance antioxidant and antiferroptosis effects. Pharmacological induction of A20 confers protective effects in AIH. The clinical correlation among A20, KEAP1, NRF2 and ferroptosis is validated in human AIH samples.

Conclusions:

Our findings elucidate a previously unrecognised A20-KEAP1-NRF2 axis that orchestrates hepatocyte ferroptosis in AIH. Targeting A20 may provide a promising therapeutic strategy for AIH.

01 Jul 2026·INTERNATIONAL IMMUNOPHARMACOLOGY

AdipoRon alleviates depression-like behaviors in mice by activating AdipoR2-JAK1-STAT3 pathway in microglia

Article

Author: Li, Tianxiang ; Cui, Dan ; Zhu, Wenhui ; Zhu, Zi ; Xie, Haier ; Chang, Jinlong ; Li, Weifen

AIM:

Major depressive disorder (MDD) is a disabling psychiatric disease featuring altered adiponectin signaling, evidenced by changes in peripheral adiponectin levels and receptor activation-both potentially predictive of treatment response. While adiponectin's therapeutic role in MDD is established, specific molecular mechanisms, particularly relating to neuroinflammation, remain unclear.

METHODS:

Used a chronic restraint stress (CRS) mouse model treated with AdipoRon (adiponectin receptor agonist). In vitro adiponectin receptor 2 (AdipoR2) knockdown in BV2 microglia and genetic AdipoR2 ablation in mice were performed. KEGG analysis compared serum metabolites from the patients with depression and controls.

RESULTS:

AdipoRon alleviated depressive-like behaviors in CRS mice, promoting hippocampal microglial polarization to the anti-inflammatory M2 phenotype and selectively increasing hippocampal interleukin-10 (IL-10). AdipoR2 knockdown in BV2 cells altered cytokine/protein profiles. AdipoRon activated hippocampal AdipoR2 expression and modulated JAK1/STAT1/STAT3 phosphorylation in CRS mice. AdipoR2 knockout induced depression-like behaviors. KEGG analysis revealed significant alterations in adiponectin-associated lipid metabolism pathways (glycerophospholipid/glycerolipid metabolism, pentose phosphate pathway) in MDD patients.

CONCLUSION:

AdipoR2 activation mediates AdipoRon's antidepressant effects via AdipoR2-dependent hippocampal microglial M2 polarization, enhanced IL-10, downstream JAK/STAT signaling, and systemic lipid metabolic adaptations. This supports AdipoRon as a promising therapeutic for stress-related depression.

100 Deals associated with AdipoRon

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diminished ovarian reserve	Preclinical	China	Guangzhou Medical University	14 Aug 2026
Breast Cancer	Preclinical	China	National Taiwan University College of Medicine	28 Apr 2025
Diabetic Cardiomyopathies	Preclinical	South Korea	The Catholic University of Korea	06 Jun 2020
Type 2 diabetes mellitus with established diabetic nephropathy	Preclinical	South Korea	The Catholic University of Korea	31 Oct 2017
Diabetes Mellitus, Type 2	Preclinical	Japan	University of Tokyo	30 Oct 2013
Obesity	Preclinical	Japan	University of Tokyo	30 Oct 2013