ABCG4 Inhibitors

Chemical inhibitors of ABCG4 can be broadly categorized into two groups based on their mode of action: direct inhibitors that interact with the transporter itself, and indirect inhibitors that modulate the protein's function by altering the physiological context in which it operates. Direct inhibitors would typically bind to the protein's substrate-binding site or its ATP-binding site, thereby preventing substrate transport or ATP hydrolysis, which is crucial for the transporter's function. Indirect inhibitors can affect the protein's function by altering the levels of its substrates or by changing the lipid composition of the membranes in which ABCG4 is embedded, which can affect transporter activity.

The ABCG4 inhibitors listed above are primarily indirect inhibitors, as they function by modulating the lipid metabolism pathways and the cellular environment to which ABCG4 responds. For example, changes in intracellular cholesterol levels brought about by statins such as lovastatin and simvastatin can indirectly inhibit ABCG4 by altering the lipid composition of membranes and potentially the availability of substrates. Similarly, compounds like fumitremorgin C, although not specific to ABCG4, can inhibit a wide range of ABC transporters by interfering with their ATPase activity. These inhibitors can be useful tools in research to understand the physiological role of ABCG4 and the impact of lipid metabolism on its function.