Mechanisms of action studies of WBI-4002, a novel drug candidate promoting epithelial integrity

促进上皮完整性的新候选药物 WBI-4002 的作用机制研究

• 批准号: 543615-2019
• 负责人: Stadnyk, Andrew
• 金额: $ 1.82万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=680871
• 关键词: Mechanisms; action; studies; WBI; 4002

The cells lining our tissue surfaces in contact with the environment are called epithelial cells. To create a barrier epithelial cells are tightly connected to each other and are sometimes stacked upon each other, like on our skin. In the intestines the epithelium is only one cell thick in order to digest and absorb food. The result is that the "tightness" can be modified by events in the host or from products arriving in the lumen. These changes in "tightness" or integrity occur during diseases like Celiac disease or Crohn's disease and ulcerative colitis. While we understand the molecules involved in epithelial integrity we don't have many products that can improve it when we may need to, but we have some clues from our the food. Certain plants in our diet are thought to have anti-inflammatory and anti-oxidant properties (blueberries, for example). As scientists worked to purify the active plant products "polyphenol stilbenes" were discovered to have health benefits. Welichem Biotech Inc. (Burnaby, BC) has developed a drug in this class they call WBI-4002. WBI-4002 is a trans-hydroxystilbene. They have learned that the drug binds a molecule on the surface of cells called the aryl hydrocarbon receptor (AhR). The AhR is present on many types of cells including on epithelial cells. Other researchers showed that when the AhR binds compatible molecules it can improve the integrity of the epithelium. Welichem Biotech Inc. wants to know if their drug can also modify the integrity of epithelium. The Company contacted Dr. Stadnyk, who is an expert on the intestinal epithelium. Dr. Stadnyk will apply WBI-4002 to intestinal epithelial cells, from humans and mice, in petri dishes, and measure any effects on integrity. He will examine the molecules that make up the bonds between cells to figure out what changes when WBI0-4002 is applied. If the drug works to improve epithelial integrity it may be a good candidate for treating inflammatory diseases of the intestines.

排列在我们组织表面与环境接触的细胞被称为上皮细胞。为了建立屏障，上皮细胞彼此紧密相连，有时相互堆叠，就像我们的皮肤上一样。在肠道中，为了消化和吸收食物，上皮只有一个细胞厚。其结果是，“密封性”可以通过主机中的事件或到达管腔的产品来修改。这些“紧密性”或完整性的变化会发生在诸如腹腔疾病、克罗恩病和溃疡性结肠炎之类的疾病中。虽然我们了解与上皮完整性有关的分子，但我们没有太多产品可以在需要的时候改善它，但我们从食物中获得了一些线索。我们饮食中的某些植物被认为具有抗炎和抗氧化的特性(例如蓝莓)。在科学家努力提纯活性植物产品时，人们发现多酚二苯乙烯类化合物对健康有好处。韦利赫姆生物技术公司(BC伯纳比)已经开发出一种他们称之为WBI-4002的药物。WBI-4002是一种反式羟基二苯乙烯。他们了解到，这种药物结合了细胞表面的一种分子，称为芳烃受体(AhR)。AhR存在于多种类型的细胞上，包括上皮细胞。其他研究人员表明，当AhR与相容的分子结合时，它可以改善上皮细胞的完整性。韦利赫姆生物技术公司想知道他们的药物是否也能改变上皮细胞的完整性。该公司联系了肠道上皮专家斯塔德尼克博士。斯塔德尼克博士将把WBI-4002应用于培养皿中来自人类和小鼠的肠道上皮细胞，并测量其对完整性的影响。他将研究构成细胞间键的分子，以找出当应用WBI0-4002时会发生什么变化。如果这种药物能改善上皮完整性，它可能是治疗肠道炎症性疾病的一个很好的候选药物。