SLC43A1 Inhibitors

Chemical inhibitors of SLC43A1 utilize various mechanisms to obstruct its glucose transport function. Phloretin and Phlorizin exhibit their inhibitory action by binding to the glucose transport site of SLC43A1, preventing glucose from entering cells through this transporter. Their mechanism involves competitive inhibition, where they mimic the structure of glucose and occupy the binding sites, leaving no room for the actual substrate. Quercetin, Apigenin, Fisetin, Luteolin, Myricetin, and Chrysin operate similarly, as they also engage in competitive inhibition with glucose for the binding sites on SLC43A1. This process reduces the transporter's affinity for glucose, thereby diminishing its transport activity. By directly binding to SLC43A1, these chemicals ensure that glucose uptake is hindered, effectively inhibiting the protein's primary function.

Furthermore, WZB117 and STF-31 target SLC43A1 by preventing the conformational changes essential for glucose translocation across the cell membrane. They bind to the glucose transporter domain and block the glucose-binding site, impeding the uptake mechanism. Biochanin A exhibits inhibition by binding to and interfering with the glucose transporter, thereby preventing the necessary structural transitions required for glucose transport. Genistein, on the other hand, indirectly influences SLC43A1 activity by modulating the phosphorylation states of proteins that regulate the transporter's activity. Although Genistein does not directly bind to the glucose transport sites, its action on protein phosphorylation results in a downstream reduction in the transport activity of SLC43A1. Collectively, these chemicals exhibit a range of interactions with SLC43A1 that lead to a decrease in its ability to transport glucose into cells, thereby effectively inhibiting the protein's function.