Peroxisome proliferator-activated receptor γ (PPARγ) is an important target for antidiabetic drug development. Ace Therapeutics aims to provide clients with comprehensive antidiabetic drug development support targeting PPARs, from target screening, drug optimization to preclinical testing.

Introduction of Peroxisome Proliferator-Activated Receptors

PPARγ belongs to the nuclear hormone receptor superfamily. Its role in the regulation of glucose homeostasis and lipid metabolism includes:

• It functions as a transcription factor to regulate genes involved in glucose metabolism and lipidhomeostasis.
• Enhances insulin sensitivity, particularly in adipose tissue and skeletal muscle.
• Enhances adipocyte differentiation and intracellular lipid storage.

Studies have shown that activation of PPARγ improves insulin resistance. PPARγ agonists (e.g., thiazolidinediones) have become important in the treatment of type 2 diabetes, and research on PPARα and PPARδ agonists has provided new therapeutic targets for antidiabetic drug development.

Fig. 1 Mechanism of PPAR. (Dhankhar, S. et al., 2023)

PPARγ-Targeted Antidiabetic Drug Development Services at Ace Therapeutics

Ace Therapeutics provides end-to-end drug development solutions, spanning target confirmation to preclinical assessment. Our mission is to empower clients in discovering next-generation PPARγ agonists with enhanced safety, efficacy, and innovation.

PPARγ target identification and mechanism study

We use a multidimensional technology platform to validate the feasibility and therapeutic potential of PPARγ as a drug target:

• Gene/protein level analysis

PPARγ gene expression assay (qPCR, RNA-seq)

Protein expression and localization (Western blot, IHC/IF)

• Functional validation

Reporter gene assay (PPRE-driven luciferase assay)

Gene knockout/knockdown experiments (using siRNA, CRISPR) to validate metabolic phenotypes

• Combined characterization

Ligand binding experiments (SPR, ITC)

Molecular docking simulations (PPARγ-LBD structure analysis)

Screening and optimization of candidate PPARγ agonists

• Structure-based drug design: We use a structure-based drug design approach, combined with virtual screening and experimental validation, to screen potential PPARγ agonists or partial agonists from large-scale compound libraries.
• Computer-aided design and drug optimization: We optimize the structure of candidate molecules by computer-aided design to improve their affinity and selectivity.
• Target optimization: We improve the binding affinity of candidate molecules with PPARγ, enhance the selectivity, reduce the off-target effects, and thus improve the safety and efficacy of the drug.

Preclinical evaluation of candidate PPARγ agonists

In the preclinical development phase of potential PPARγ agonists, we systematically evaluate both therapeutic efficacy and safety profiles using established in vitro assays and validated animal models.

In vitro experiments

• Cell transactivation assay
• Protein-protein interaction analysis
• Molecular dynamics simulation

In vivo experiments

• Metabolic function testing in animal models
• Pharmacokinetic studies
• Toxicological evaluation

Advantages of Our PPARγ-Targeted Antidiabetic Drug Development Services

• Multidisciplinary technology integration

Combining advanced molecular biology techniques, computer-aided design and interdisciplinary collaboration, we provide comprehensive solutions.

• Innovative drug development

We are committed to developing safe, effective and novel PPARγ agonists to provide better treatment options for patients with type 2 diabetes.

• Full-service support

We provide a full range of services from target identification and mechanistic studies, screening and optimization of agonist candidates to preclinical evaluation.

Ace Therapeutics is committed to helping clients overcome R & D bottlenecks and accelerate project progress with scientific rigor and flexible, customized services. Please contact us for more details and we will be happy to assist you.

Reference

1. Dhankhar, S.; et al. Novel targets for potential therapeutic use in Diabetes mellitus. Diabetology & Metabolic Syndrome. 2023, 15(1): 17.

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• Mouse Models
• Assay Kits
• Antibodies
• Cell Lines & Lysates
• Proteins & Peptides
• Inhibitors & Activators