Sandbox Reserved 1606: Difference between revisions

Dysfunctions in ABCG2 are linked to hyperuricemia which can lead to gout, kidney disease, and hypertension, all of which are thought to be the result of impaired transport of uric acid. Additionally, the expression of ABCG2 correlates to poor prognosis and treatment outcome of certain cancers such as breast, ovarian, and lung.<ref name="Jackson"/>

ABCG2 hinders cancer treatment by contributing to [https://en.wikipedia.org/wiki/Multiple_drug_resistance multidrug resistance] in tumor cells.  ABCG2 exports xenbiotics, including vital anti-cancer drugs, which results in the inability to treat cancer cells.  The inhibition of ABCG2 would stop the transport of anti-cancer drugs out of cancer cells.  Due to the potential of ABCG2 inhibition to aid in cancer treatment, efforts have been made to develop specific inhibitors of ABCG2 and other ABC transporters.  Some promising inhibitors were derived from fungal toxin fumitremorgin C; however, many of those derivatives developed have neurotoxic effects.<ref name="Jackson"/>

===ABCG2 Inhibitors===  

<scene name='83/832932/Inhibitor_bound_cavity_1/1'>Inhibitors bind Cavity 1</scene>, acting as competitive inhibitors against ABCG2 substrates. Depending on the size of the inhibitor, one or two molecules are required to bind 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"/>