NDST4 Inhibitors

Chemical inhibitors of NDST4 function through various mechanisms to impede its sulfotransferase activity. Suramin operates by obstructing growth factor receptors and enzymatic activities that are crucial for the sulfation processes that NDST4 catalyzes. When growth factor receptors are inhibited, the sulfotransferase activity of NDST4 is compromised, leading to a decrease in its functional output. Chlorate acts as a competitor to sulfate uptake, thereby restricting the availability of the sulfate donor PAPS essential for NDST4 activity; this competitive inhibition leads to a reduction in the enzyme's sulfation capacity. Methylthiouracil, through its action on thyroid hormone synthesis, can lead to a decrease in systemic sulfation capacity, which in turn can limit the availability of sulfate pools for NDST4 activity. Bisphenol A can disrupt the sulfotransferase activity by binding directly to the active site of sulfotransferase enzymes, potentially leading to direct interference with the catalytic process of NDST4. In addition to these inhibitors, compounds like Quercetin and Triclosan exhibit their inhibitory effects by competing with PAPS or by altering the enzyme's structure, respectively, thus impeding NDST4's enzymatic function. Ellagic acid and Pentachlorophenol are also known to bind to the active site or critical regions of the enzyme, leading to a decrease in NDST4's sulfotransferase activity. Similarly, Chlorpromazine and Desipramine can inhibit NDST4 by changing the enzyme's conformation or by interacting with its active site. Miconazole, while primarily known as an inhibitor of cytochrome P450 enzymes, has been shown to inhibit sulfotransferase enzymes, including NDST4, by engaging with the enzyme's active site. Lastly, Ketoconazole, through its inhibition of cytochrome P450 enzymes, can indirectly influence the sulfation processes, thereby affecting the activity of NDST4. The collective action of these inhibitors leads to a substantial reduction in NDST4's ability to transfer sulfate groups to its substrates.