ABCA14 Inhibitors

Chemical inhibitors of ATP-binding cassette, sub-family A member 14 (ABCA14) encompass a variety of molecules that impede the protein's function through distinct mechanisms of action. Verapamil, a calcium channel blocker, can inhibit ABCA14 by hindering the ATP-driven conformational changes necessary for substrate transport across cellular membranes. This disruption can effectively immobilize the transporter in an inactive state. Quercetin, as a naturally occurring flavonoid, can inhibit ABCA14 by either stabilizing an inactive conformation of the protein or by interfering with the ATPase activity, which is crucial for the transport cycle. Similarly, Valspodar and Elacridar work by competitive and non-competitive inhibition, respectively; Valspodar competes with natural substrates of ABCA14, while Elacridar binds to recognition sites on the protein, blocking the transport pathway.

Continuing with this theme, Tariquidar can inhibit ABCA14 by binding to allosteric sites that modulate the transporter's conformation and ATPase activity. Zosuquidar targets the nucleotide-binding domain, impeding the ATP hydrolysis cycle vital to the transporter's activity. Laniquidar interacts with the transmembrane domains to alter the transporter's conformation, which inhibits substrate translocation. On the other hand, Reserpine can inhibit ABCA14 by occupying the substrate-binding pocket, which prevents substrates from accessing the transport pathway. Progesterone interacts with regulatory sites on ABCA14, which can inhibit the ATP hydrolysis and transport cycle. Cyclosporine A directly binds to the ATP-binding site of ABCA14, inhibiting ATP hydrolysis and thereby the transport mechanism. Glibenclamide inhibits ABCA14 by obstructing the ATP-binding cassette sites critical for the catalytic activity that drives substrate transport. Lastly, Rifampicin can inhibit ABCA14 by preferentially binding to the substrate-binding sites or the nucleotide-binding domains, disrupting the transport cycle and effectively inhibiting the protein's function.