Claudin-18 is a member of the claudin family of proteins, which are integral components of tight junctions in epithelial and endothelial cell layers. These tight junctions control the paracellular transport between cells, contributing to the selective permeability and integrity of barriers such as the gastric mucosa. Claudin-18 has specific isoforms, such as claudin-18.2, which is primarily expressed in the stomach lining and plays a critical role in maintaining the gastric barrier and acid-base homeostasis.
The chemical class designed to inhibit claudin-18, referred to here as BLANK claudin-18 inhibitors, includes molecules that disrupt the normal function of claudin-18. These inhibitors can act through direct binding to claudin-18, altering its ability to interact with other claudin proteins or with accessory proteins necessary for the formation of functional tight junctions. By binding to claudin-18, these inhibitors can induce conformational changes that destabilize tight junctions, increasing paracellular permeability. This effect on claudin-18 can be exploited in research to study the physiological consequences of compromised tight junction integrity and to understand the protein's role in various cellular processes, such as barrier function and cellular polarity. Alternatively, BLANK claudin-18 inhibitors may function indirectly by modulating the expression levels or the post-translational modifications of claudin-18. These compounds may influence intracellular signaling pathways that regulate the transcription or translation of claudin-18 or its insertion into the cell membrane. Other indirect inhibitors might affect the protein turnover of claudin-18, promoting its degradation or preventing its proper trafficking to tight junctions.
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