Delving into the Latest Updates on PPARγ antagonists(AstraZeneca) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

compound 10(AstraZeneca)

Target

PPARγ

Action

antagonists

Mechanism

PPARγ antagonists(Peroxisome proliferator-activated receptor γ antagonists)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication

Diabetes Mellitus

Inactive Indication-

Originator Organization

AstraZeneca PLC

Active Organization

AstraZeneca PLC

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC22H14Cl2N2O4

InChIKeyIQKNCBUBONVBNJ-UHFFFAOYSA-N

CAS Registry2882975-84-8

Nephrolithiasis is a significant health issue causing pain, hypertension, and chronic kidney disease. Phillyrin, a bioactive compound from Forsythia suspensa, may offer therapeutic benefits against these conditions. The study was focused on phillyrin efficacy on alleviating kidney stone formation and associated damage.

METHODS:

HK-2 cells were exposed to calcium oxalate (CaOx) to generate an in vitro kidney cell injury model. The kidney stones were induced in rats by 1% ethylene glycol and 2% ammonium chloride. Cell viability was assessed by CCK-8 assay. Cell apoptosis was detected by JC-1 mitochondrial membrane potential assay. ROS and MDA contents and the activity of SOD and GSH-Px were assayed using matched assay kits. Differentially expressed genes (DEGs) were identified by RNA sequencing (RNA-seq).

RESULTS:

Phillyrin significantly reduced CaOx-induced apoptosis and oxidative stress in HK-2 cells. Moreover, phillyrin repressed oxidative stress and renal crystal deposition in model rats of kidney stones. RNA-seq revealed DEGs in rat kidneys post-phillyrin treatment, suggesting involvement in key pathways. Phillyrin activated the PPARγ signaling pathway in kidney stone induced rats and CaOx-exposed HK-2 cells. Furthermore, the PPARγ antagonist GW9662 exerted a counteracting impact on phillyrin-mediated anti-apoptosis and anti-oxidative effects in CaOx-exposed HK-2 cells.

CONCLUSION:

The present study demonstrated that the potential efficacy of phillyrin on alleviating CaOx kidney stone formation and associated oxidative stress. PPARγ signaling is the possible mechanism of action of phillyrin in controlling nephrolithiasis-triggered apoptosis.

01 Dec 2025·CELLULAR IMMUNOLOGY

Exosomes from hypoxic pretreated BMSCs attenuate primary Sjögren's syndrome-induced skin injury via PPARγ-mediated M2-like macrophage activation

Article

Author: Sun, Chao ; Wang, Yuan ; Wang, Xin ; Xu, Guixia ; Jin, Mingming ; Yang, Xinmeng ; Sun, Xu

BACKGROUND:

Sjögren's syndrome (SS) is an autoimmune disorder identified by a triad of sicca symptoms, pain, and fatigue. SS-induced skin injury seriously affects people's health but remains unsolved. Accumulating investigations have confirmed that exosomes (Exos) originating from bone marrow mesenchymal stem cells (BMSCs) can bolster the stressed microenvironment and tissue repair. Present study aimed to unravel therapeutic effects regarding BMSC Exos on SS-induced skin injury.

METHODS:

In this study, an SS mouse model was constructed, and exosomes from BMSCs (Exos) and hypoxic pretreated BMSCs (HExos) were isolated. The therapeutic effects of exosomes in SS were identified using ELISA, immunohistochemistry, and immunofluorescence. High-throughput sequencing (HTS) was utilized to characterize differentially expressed genes between Exos and HExos.

RESULTS:

The data showed that Exos, especially HExo treatments, affected the inhibition of SS-induced inflammatory factor expression, cell apoptosis, ROS deposition, and collagen loss. HTS and RT-qPCR detection showed PPARγ functioned importantly for HExo-mediated protective effects against SS-induced skin injury. The in vitro experiment using RAW confirmed that PPARγ expression inhibited LPS-induced M1-like macrophage activation, which was confirmed using the PPARγ antagonist T0070907. PPARγ upregulation improved therapeutic effects regarding Exos upon skin injury in SS mice by promoting M2-like macrophage activation.

CONCLUSION:

Taken together, our study found that exosomes from hypoxic pretreated BMSCs attenuated primary Sjögren's syndrome-induced skin injury via PPARγ delivery and promoted M2-like macrophage activation.

01 Dec 2025·COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY

GW-9662, a peroxisome proliferator-activated receptor γ (PPARγ) inhibitor, impairs early embryonic development in zebrafish

Article

Author: Battu, Jabez Raju ; Pathirajage, Kanchaka Senarath ; Johnson, Tyler ; Dasgupta, Subham ; Sharma, Sunil

Peroxisome proliferator-activated receptor γ (PPARγ) functions as a nuclear transcription factor with primary roles in lipid and glucose metabolism and adipocyte differentiation. Despite intensive research in metabolic contexts, its role during early vertebrate development remains underexplored. Our study focused on understanding PPARγ's developmental role by using a PPARγ antagonist, GW-9662 (GW), in zebrafish embryos. We exposed embryos to GW from 6 hours post-fertilization (hpf) to 24 hpf and observed that the embryos were ventralized by 24 hpf. Western Blot and immunohistochemistry for PPARγ protein demonstrated that GW-mediated PPARγ inhibition may be localized within the embryos. Transcriptomic analysis revealed that exposure to GW led to dysregulation of multiple biological pathways, including cytoskeletal organization, lipid biosynthesis, and epithelial-to-mesenchymal transition (EMT). Immunohistochemistry further validated these findings, demonstrating increased lipid accumulation, cytoskeletal disruption, and altered EMT markers. Our findings suggest that while GW plays a crucial role in multiple physiological processes during early embryogenesis, further research is needed to examine if these impacts are mediated by PPARγ.

100 Deals associated with PPARγ antagonists(AstraZeneca)

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