BST-1 Inhibitors

Chemical inhibitors of BST-1 can act through various mechanisms to impede the protein's functional activity, primarily targeting its role as a NAD glycohydrolase and ADP-ribosyl cyclase. Piceatannol and Apigenin are two such inhibitors that can inhibit BST-1 by reducing the availability of NAD+, which is an essential substrate for BST-1's enzymatic functions. Piceatannol achieves this by inhibiting the activity of CD38, a protein structurally related to BST-1 and involved in NAD+ metabolism. Apigenin, known for its CD38 inhibition, may similarly affect BST-1, given their functional parallels. Nicotinamide, serving as a non-competitive inhibitor, can occupy the NAD+ binding site or disrupt the catalytic activity of BST-1, while Flavopiridol, with its broad kinase inhibition properties, can also inhibit BST-1 through similar mechanisms.

Other chemicals can exert their inhibitory effects on BST-1 by influencing the cellular levels of NAD+ or interfering with BST-1's ability to interact with its substrate. FK866, a potent inhibitor of nicotinamide phosphoribosyltransferase (NAMPT), can reduce NAD+ levels in cells, thus indirectly inhibiting the activity of BST-1 by substrate deprivation. Cladribine, although primarily used to disrupt nucleotide synthesis, can also affect BST-1 activity by altering NAD+ availability or through structural mimicry. Zinc, in excess, can inhibit BST-1 by binding to the enzyme and interfering with its normal function. Gallotannin, a known inhibitor of other ADP-ribosyl cyclases, can bind to the active site of BST-1, thus inhibiting its enzymatic action on NAD+. Kuromanin chloride, by inhibiting CD38, suggests a possible route to BST-1 inhibition due to the shared NAD glycohydrolase activity between the two proteins.