Authors:

Ricardo De La Fuente, Wan Namkung, Aaron Mills, A. S. Verkman

Journal Information:

Molecular Pharmacology, March 2008, Volume 73, Issue 3, Pages 758-768

Abstract:

This paper describes a high-throughput screening study aimed at identifying inhibitors of human intestinal calcium-activated chloride channels (CaCCs). CaCCs play an important role in intestinal fluid secretion and other physiological functions. Using a high-throughput screening method, the authors identified several compounds from a chemical library that could inhibit CaCCs, and described their inhibitory effects and potential applications in detail.

摘要:

这篇文章描述了一项筛选小分子的研究，旨在发现人类肠道钙激活氯通道（CaCCs）的抑制剂。CaCCs在肠道液体分泌和其他生理功能中起重要作用。通过高通量筛选方法，作者们从一个化合物库中筛选出了多种能够抑制CaCCs的化合物，并详细描述了这些化合物的抑制效果及其潜在的应用。

Research Methods:

- High-throughput Screening: A fluorescence-based screening method was used to identify potential CaCC inhibitors from a chemical library.
- Electrophysiology Assays: Whole-cell patch-clamp techniques were used to measure the inhibitory effects of the compounds on CaCCs.
- Structure-Activity Relationship Analysis: The relationship between the chemical structures of the compounds and their inhibitory activities was studied.

研究方法:

- 高通量筛选: 使用一种基于荧光的筛选方法，从一个化合物库中筛选出潜在的CaCCs抑制剂。
- 电生理学测定: 通过全细胞膜片钳技术测量化合物对CaCCs的抑制效果。
- 结构活性关系分析: 研究了不同化合物的结构与其抑制活性之间的关系。

Major Findings:

1. Identification of Inhibitors: Several effective CaCC inhibitors were identified and their chemical structures were characterized.
2. Inhibitory Effects: The inhibitory effects of these inhibitors on CaCCs were evaluated in detail, with several compounds showing high inhibitory activity.
3. Potential Applications: These inhibitors may have potential applications in the treatment of CaCC-related diseases such as cystic fibrosis and intestinal secretion disorders.

主要发现:

1. 抑制剂的鉴定: 筛选出几种有效的CaCCs抑制剂，并对其化学结构进行了表征。
2. 抑制效果: 详细评估了这些抑制剂对CaCCs的抑制效果，发现其中几种化合物表现出高效的抑制活性。
3. 潜在应用: 这些抑制剂可能在治疗与CaCCs相关的疾病，如囊性纤维化和肠道分泌失调方面具有潜在的应用前景。

Conclusion:

This study provides important clues for the future development of new CaCC inhibitors and opens new avenues for the treatment of related diseases.

结论:

这项研究为未来开发新的CaCCs抑制剂提供了重要的线索，并为相关疾病的治疗开辟了新的途径。

Key Compounds and CAS Numbers:

1. CaCCinh-A01: CAS No. 344458-15-7
2. Niflumic acid: CAS No. 4394-00-7