At Ace Therapeutics, we possess a deep understanding of the role of chloride channel protein 2 (ClC-2) in regulating gastrointestinal barrier function under various pathophysiological conditions. We help customers design and optimize ClC-2 activators to enhance chloride transport and restore intestinal mucosal barrier function impaired by epithelial damage, such as apoptosis, erosion, and ulceration. Our dedicated team excels in target validation, lead compound optimization, preclinical pharmacodynamic studies, and formulation development, all aimed at maximizing the therapeutic potential of ClC-2 activators.
The Role of ClC-2 in Gastrointestinal Diseases
Chloride channel protein 2 (ClC-2) is a voltage-gated chloride channel that plays a significant role in regulating chloride ion transport across epithelial cells in the gastrointestinal (GI) tract. ClC-2 helps maintain fluid and electrolyte balance, which is crucial for proper digestive function and intestinal barrier integrity. Dysregulation or mutations in ClC-2 have been implicated in various gastrointestinal diseases, including congenital chloride diarrhea and other forms of chronic diarrhea. As a result, ClC-2 represents a promising drug target.
Figure 1. The role of ClC-2 chloride channels in regulating intestinal barrier function. (Jin Y., Blikslager A.T., 2015)
What Can We Do for the Development of ClC-2 Activators?
Our target validation services evaluate whether ClC-2 is a viable target for therapeutic intervention. We utilize advanced techniques such as RNA sequencing, immunohistochemistry, and functional assays to investigate the expression and function of ClC-2 in different types of gastrointestinal and liver tissues and cell, helping customers understand the role of ClC-2 in specific diseases and how ClC-2 activity is altered in various gastrointestinal diseases.
- Pharmacodynamic Evaluation of Chloride Channel Activators
At Ace Therapeutics, we offer comprehensive in vitro and in vivo pharmacology services for the development of chloride channel protein 2 activators. Our services are designed to evaluate the efficacy, safety, and mechanism of action of ClC-2 activators in various models of gastrointestinal diseases.
In Vitro Pharmacodynamic Services
In Vivo Pharmacodynamic Services
Our in vitro pharmacodynamic services encompass a range of assays to support the development of novel chloride channel activators.
- Ussing Chamber Assays: We use Ussing chambers to measure chloride ion flux across epithelial cell layers, allowing us to assess the effects of candidate activators on ClC-2-mediated chloride secretion.
- Patch-Clamp Electrophysiology: We perform patch-clamp electrophysiology experiments to investigate the effects of your activators on ClC-2 channel gating and conductance.
- Calcium Imaging Assays: We utilize calcium imaging techniques to assess the effects of your activators on intracellular calcium levels, which can influence ClC-2 channel activity.
We utilize a variety of animal models to evaluate the efficacy of your ClC-2 activators in vivo.
- Diarrhea Models: We employ animal models of diarrhea, such as castor oil-induced diarrheal mice, to evaluate the ability of your activators to reduce fluid secretion and improve stool consistency.
- Inflammatory Bowel Disease (IBD) Models: We utilize animal models of IBD, such as the dextran sulfate sodium (DSS)-induced colitis mouse models, to evaluate the ability of your activators to reduce inflammation and tissue damage.
- Pharmacokinetic Studies on Chloride Channel Activators
We conduct pharmacokinetic studies in animals to determine the absorption, distribution, metabolism, and excretion (ADME) of your ClC-2 activators, informing optimal dosing regimens and formulation strategies.
If you are developing CIC-2 activator and requiring an experienced partner to support your preclinical studies, please contact us. Ace Therapeutics is eager to discuss how our tailored approach and full-service capabilities can support your therapeutic development needs and drive innovation in gastroenterology.
References
- Jin Y., Blikslager A.T. ClC-2 regulation of intestinal barrier function: Translation of basic science to therapeutic target. Tissue Barriers. 2015, 3(4):e1105906.
- Park Y.S., et al. The ClC-2 chloride channel activator, Lubiprostone, improves intestinal barrier function in biopsies from Crohn's disease but not ulcerative colitis patients. Pharmaceutics. 2023, 15(3):811.
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