Ace Therapeutics offers a comprehensive suite of services to support the development of phosphodiesterase (PDE) inhibitors targeting a range of gastrointestinal and liver diseases. We leverage our expertise in PDE biology, disease pathogenesis, and drug discovery to help researchers design and optimize PDE inhibitors with enhanced efficacy, selectivity, and safety profiles.
The Role of Phosphodiesterase in GI and Liver Diseases
Phosphodiesterases (PDEs) are a group of enzymes that play a critical role in cellular signaling by regulating the levels of cyclic nucleotides, such as cyclic AMP (cAMP) and cyclic GMP (cGMP). In gastrointestinal and liver diseases, dysregulation of PDE activity can lead to aberrant signaling pathways that contribute to diseases such as inflammatory bowel disease (IBD), liver fibrosis, and liver cirrhosis. Targeting specific PDE isoforms offers a promising therapeutic strategy, as PDE inhibitors can modulate these signaling pathways to reduce inflammation, prevent tissue damage, and promote tissue repair.
Figure 1. Effects of phosphodiesterase 4 (PDE4) inhibitors on the inflamed intestinal mucosa. (Spadaccini M., et al., 2017)
What Can We Do for the Development of Phosphodiesterase Inhibitors?
- Research on PDE Isoforms in Gastroenterology & Hepatology
| Items |
Service Details |
| Target Validation & Profiling |
We utilize techniques such as RNA sequencing and quantitative PCR to assess the expression levels of different PDE isoforms in different types of cells and tissues associated with gastrointestinal and liver diseases. |
| Functional Studies |
We can conduct functional studies in cell lines and animal models to investigate the role of specific PDE isoforms in disease pathogenesis. |
| Signaling Pathway Analysis |
We help researchers investigate the downstream signaling pathways activated by specific PDE isoforms, including their role in regulating intracellular cAMP and cGMP levels. |
- In Vitro Pharmacodynamic Studies of PDE Inhibitors
We conduct in vitro studies using relevant cell lines and assays to evaluate the efficacy, selectivity, and mechanism of action of your PDE inhibitors.
- Enzyme Activity Assays: Measure the ability of PDE inhibitors to inhibit the enzymatic activity of specific PDE isoforms.
- cAMP/cGMP Accumulation Assays: Measure the ability of PDE inhibitors to increase intracellular cAMP or cGMP levels by inhibiting PDE activity.
- Cell Signaling Assays: Assess the effect of PDE inhibitors on downstream signaling pathways, such as the MAPK pathway, NF-κB pathway, and JAK-STAT pathway.
- Cytokine Production Assays: Measure the ability of PDE inhibitors to modulate the production of inflammatory cytokines, such as TNF-α, IL-6, and IL-1β.
- Cell Proliferation and Apoptosis Assays: Assess the impact of PDE inhibitors on cell proliferation, differentiation, and apoptosis.
- In Vivo Pharmacodynamic Studies of PDE Inhibitors
We conduct preclinical studies in animal models of gastrointestinal and liver diseases to assess the efficacy and safety of PDE inhibitors.
| Selection of Animal Models |
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| Evaluation of Drug Efficacy |
- Histological Analysis: Assess inflammation, ulceration, tissue damage, and fibrosis.
- Cytokine Profiling: Measure levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the colon, liver, and serum.
- Gene Expression Analysis: Assess the expression of genes involved in inflammation, fibrosis, and cell function.
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Ace Therapeutics provides a wide range of specialized services for the development of PDE inhibitors. Whether you're seeking assistance with target validation, lead compound optimization, preclinical testing, or formulation design, Ace Therapeutics has the expertise to support your PDE inhibitor development program. Contact us today to discuss your specific needs and obtain a detailed quote.
References
- Spadaccini M., et al. PDE4 Inhibition and inflammatory bowel disease: A novel therapeutic avenue. Int J Mol Sci. 2017, 18(6):1276.
- El-Deen R.M., et al. Comparative effectiveness of phosphodiesterase 3, 4, and 5 inhibitors in amelioration of high-fat diet-induced nonalcoholic fatty liver in rats. Fundam Clin Pharmacol. 2020, 34(3):353-364.
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