At Ace Therapeutics, we specialize in the development of Na+/H+ exchanger (NHE) inhibitors. Our experts with deep expertise in NHE research and drug discovery, provide comprehensive services for the development of potent and selective NHE inhibitors for the treatment of inflammatory bowel disease, colorectal and gastric cancer, non-alcoholic fatty liver disease (NAFLD), liver fibrosis and other digestive diseases.
NHEs in Gastroenterology and Hepatology
NHEs are essential membrane proteins that regulate cellular pH and volume, playing crucial roles in various physiological processes. Dysregulation of NHE activity is increasingly recognized as a key factor in the pathogenesis of gastrointestinal and liver diseases. For instance, NHEs are implicated in NAFLD and liver fibrosis through lipid metabolism and HSC activation. Moreover, NHE1 promotes tumor growth and metastasis in digestive system malignancies, and NHE3 is involved in fluid absorption in the intestine, and its dysregulation contributes to diarrhea and constipation. Targeting NHEs with specific inhibitors offers potential therapeutic strategies for the treatment of a range of gastrointestinal and liver diseases.
Figure 1. NHEs related to gastrointestinal and hepatic diseases. (Cao L., et al., 2020)
What Can We Do for the Development of NHE Inhibitors?
We begin by identifying and characterizing the specific NHE isoforms involved in your target disease. This is crucial for developing highly selective inhibitors that target the relevant NHE isoform, minimizing off-target effects and potential side effects. We employ advanced techniques such as RNA sequencing, proteomics, and functional assays to identify the key NHE isoform in your disease of interest.
- Screening and Evaluation of Potential NHE Inhibitors
We utilize a variety of in vitro assays to screen and evaluate potential NHE inhibitors.
| Items |
Service Introduction |
| Functional Assays |
Measure the activity of NHE isoforms in cell lines and isolated membrane preparations. |
| Binding Assays |
Determine the affinity and selectivity of inhibitors for NHE isoforms. |
| Cell-Based Assays |
Investigate the effects of NHE inhibition on cell growth, proliferation, apoptosis, and other relevant cellular processes using various established cell lines relevant to your project. |
- In Vivo Pharmacodynamic Studies of NHE Inhibitors
| GI and Liver Disease |
Service Introduction |
| Dextran Sulfate Sodium (DSS)-induced Colitis |
Evaluate the effects of NHE inhibitors on inflammation, ulceration, and healing processes in the colon. |
| TNBS-induced Colitis |
Assess the therapeutic potential of NHE inhibitors in modulating immune responses and reducing colonic inflammation. |
| Non-Alcoholic Fatty Liver Disease |
Use high-fat diet-induced models to study the impact of NHE inhibitors on liver steatosis, inflammation, and fibrosis. |
| Liver Fibrosis Models |
Employ chemical-induced (e.g., CCl4) and bile duct ligation models to examine the effects of NHE inhibitors on hepatic stellate cell activation and fibrosis progression. |
| Hepatocellular Carcinoma (HCC) |
Test the efficacy of NHE inhibitors in reducing tumor growth and metastasis using xenograft and orthotopic HCC models. |
| Pancreatic Ductal Adenocarcinoma (PDAC) |
Evaluate the potential of NHE inhibitors to inhibit tumor growth, invasion, and metastasis in PDAC models |
- Mechanism of Action Studies
| Items |
Service Introduction |
| Analysis of Intracellular pH Modulation |
Assess how NHE inhibitors alter intracellular pH and ion exchange in target tissues. |
| Biomarker Analysis |
Identify and quantify biomarkers associated with disease progression and response to NHE inhibition. |
| Analysis of Drug Combinations |
Evaluate the efficacy of NHE inhibitors in combination with other therapeutic agents (e.g., chemotherapy, immunotherapy). |
Ace Therapeutics is dedicated to helping researchers develop innovative NHE inhibitors for the treatment of gastrointestinal and liver diseases. Our services encompass the entire preclinical development pipeline, including target identification and validation, preclinical efficacy studies, and formulation development. Contact us now to find out how our capabilities can support your project.
References
- Cao L., et al. (Patho-)Physiology of Na+/H+ exchangers (NHEs) in the digestive system. Front Physiol. 2020, 10:1566.
- Li T., Tuo B. Pathophysiology of hepatic Na+/H+ exchange (Review). Exp Ther Med. 2020, 20(2):1220-1229.
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