Sandbox Reserved 1606: Difference between revisions
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Kol143 (Figure 3) is a compound derived from [https://en.wikipedia.org/wiki/Fumitremorgin fungal toxin fumitremorgin C] (FTC), a selective inhibitor of ABCG2 which exhibits undesirable neurotoxic effects.<ref name="Allen"/> Kol143 was found to be less toxic and more potent than FTC; however, this inhibitor is nonselective toward ABCG2.<ref name="Weidner"/> Various inhibitors were derived from Kol143 with changes made at positions 1 and 2 in Figure 3, which are carbons 3 and 9 respectively. Modifications at these positions prove to affect the inhibitory capacities of compounds. A promising compound which has shown a high degree of potency is the inhibitor MZ29 (Figure 3).<ref name="Jackson"/> | Kol143 (Figure 3) is a compound derived from [https://en.wikipedia.org/wiki/Fumitremorgin fungal toxin fumitremorgin C] (FTC), a selective inhibitor of ABCG2 which exhibits undesirable neurotoxic effects.<ref name="Allen"/> Kol143 was found to be less toxic and more potent than FTC; however, this inhibitor is nonselective toward ABCG2.<ref name="Weidner"/> Various inhibitors were derived from Kol143 with changes made at positions 1 and 2 in Figure 3, which are carbons 3 and 9 respectively. Modifications at these positions prove to affect the inhibitory capacities of compounds. A promising compound which has shown a high degree of potency is the inhibitor MZ29 (Figure 3).<ref name="Jackson"/> | ||
ABCG2 inhibitors,<scene name='83/832932/Inhibitor_bound_cavity_1/ | ABCG2 inhibitors,<scene name='83/832932/Inhibitor_bound_cavity_1/2'>such as MZ29</scene>, bind Cavity 1 and act as competitive inhibitors against ABCG2 substrates and show a higher affinity toward the transporter. 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"/> | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
