Sandbox Reserved 1606: Difference between revisions
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===Inhibitors=== | ===Inhibitors=== | ||
Due to the potential for ABCG2 inhibition to aid in cancer treatment, efforts have been made to develop specific inhibitors of ABCG2 and other ABC transporters. The ABC transporter ABCB1, also known as multidrug resistance 1 (MDR1), was a therapeutic target in previous studies which produced three generations of MDR1 inhibitors, such as [https://en.wikipedia.org/wiki/Verapamil verapamil], [https://en.wikipedia.org/wiki/Valspodar valspodar], and [https://en.wikipedia.org/wiki/Zosuquidar zosuquidar]; however, many of these inhibitors had neurotoxic effects that discouraged their use as anticancer drugs.<ref name="Leonard"/><ref name="Binkhathlan"/><ref name="Witherspoon"/> | |||
ABCG2 <scene name='83/832932/Inhibitor_bound_cavity_1/1'>inhibitors</scene> that bind Cavity 1, acting as competitive inhibitors against ABCG2 substrates. Depending on the size of the inhibitor, one or two molecules can accommodate binding to the cavity and form <scene name='83/832932/Inhibitor_intxns_cavity1/1'>hydrogen bonds, van der Waals, and stacking interactions</scene> within the binding site.<ref name="Jackson"/> Many inhibitors are too big to be transported via the leucine plug resulting in the "clogging" of the transporter. With inhibitors acting as wedges, ABCG2 is locked in the inward-facing conformation and unable to transport molecules out of the cell.<ref name="Manolaridis"/> | ABCG2 <scene name='83/832932/Inhibitor_bound_cavity_1/1'>inhibitors</scene> that bind Cavity 1, acting as competitive inhibitors against ABCG2 substrates. Depending on the size of the inhibitor, one or two molecules can accommodate binding to the cavity and form <scene name='83/832932/Inhibitor_intxns_cavity1/1'>hydrogen bonds, van der Waals, and stacking interactions</scene> within the binding site.<ref name="Jackson"/> Many inhibitors are too big to be transported via the leucine plug resulting in the "clogging" of the transporter. With inhibitors acting as wedges, ABCG2 is locked in the inward-facing conformation and unable to transport molecules out of the cell.<ref name="Manolaridis"/> | ||
