Peroxisome proliferator-activated receptor γ (PPARγ) is an importanttarget for antidiabetic drug development. Ace Therapeutics aims toprovide clients with comprehensive antidiabetic drugdevelopment support targeting PPARs, from target screening, drug optimizationto preclinical testing.

Introduction of Peroxisome Proliferator-ActivatedReceptors

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

• It functions as atranscription factor to regulate genes involved in glucose metabolism and lipidhomeostasis.
• Enhances insulinsensitivity, particularly in adipose tissue and skeletal muscle.
• Enhances adipocytedifferentiation and intracellular lipid storage.

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

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

PPARγ-Targeted Antidiabetic Drug Development Services atAce Therapeutics

Ace Therapeutics provides end-to-end drug development solutions, spanningtarget confirmation to preclinical assessment. Our mission is to empowerclients 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 feasibilityand therapeutic potential of PPARγ as a drug target:

• Gene/protein levelanalysis

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) tovalidate metabolic phenotypes

• Combinedcharacterization

Ligand binding experiments (SPR, ITC)

Molecular docking simulations (PPARγ-LBD structure analysis)

Screening and optimization of candidate PPARγ agonists

• Structure-based drugdesign: We use a structure-based drug design approach, combined with virtualscreening and experimental validation, to screen potential PPARγ agonists orpartial agonists from large-scale compound libraries.
• Computer-aided designand drug optimization: We optimize the structure of candidate molecules bycomputer-aided design to improve their affinity and selectivity.
• Target optimization: Weimprove the binding affinity of candidate molecules with PPARγ, enhance theselectivity, 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, wesystematically evaluate both therapeutic efficacy and safety profiles usingestablished in vitro assays and validated animal models.

In vitro experiments

• Cell transactivationassay
• Protein-proteininteraction analysis
• Molecular dynamicssimulation

In vivo experiments

• Metabolic functiontesting in animal models
• Pharmacokinetic studies
• Toxicological evaluation

Advantages of Our PPARγ-Targeted Antidiabetic DrugDevelopment Services

• Multidisciplinarytechnology integration

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

• Innovative drugdevelopment

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

• Full-service support

We provide a full range of services from target identification andmechanistic studies, screening and optimization of agonist candidates topreclinical evaluation.

Ace Therapeutics is committed to helpingclients overcome R & D bottlenecks and accelerate project progress withscientific rigor and flexible, customized services. Please contact us for more details and we will be happy toassist you.

Reference

1. Dhankhar, S.; et al. Novel targetsfor 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