ABCG2 Inhibitors

ABCG2 inhibitors are a class of chemical agents that target the ATP-binding cassette sub-family G member 2 (ABCG2) protein, which is an integral membrane protein functioning as a transporter. ABCG2, often referred to as breast cancer resistance protein (BCRP), is part of the larger family of ATP-binding cassette (ABC) transporters that utilize the energy from ATP hydrolysis to translocate various substrates across cellular membranes. The activity of ABCG2 is critical for the efflux of a wide range of substrates, including metabolic products, xenobiotics, and certain endogenous compounds, across extra- and intra-cellular membranes. ABCG2 inhibitors are designed to bind to the protein and interfere with its substrate recognition or ATPase activity, ultimately modulating the efflux function of the transporter. These inhibitors can be structurally diverse and include small molecules that are characterized by their ability to interfere with the normal activity of ABCG2, either by direct interaction with the substrate-binding sites or by hindering the conformational changes necessary for the transport cycle. The development of ABCG2 inhibitors is a complex process that involves a deep understanding of the structure and function of the transporter. The transmembrane domains of ABCG2 contain the substrate binding pockets, and the nucleotide-binding domains are responsible for ATP binding and hydrolysis, driving the conformational changes that facilitate substrate transport. Inhibitors may act by competing with natural substrates for binding to the transmembrane domains or by noncompetitively binding to allosteric sites that modulate transporter activity.