Sandbox Reserved 1626: Difference between revisions

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== Regulation/Inhibition ==

Uptake of calcium into the mitochondria is pivotal for signalling and bioenergetic processes, but overload of calcium causes release of cytochrome c, overproduction of reactive oxygen species (ROS), swelling of the mitochondria, and opening of the mitochondrial permeability transition pore (mPTP) which all contribute to cell death. Therefore, the MCU has become a target of interest for therapies for certain conditions (like the ones above).<ref name="Woods" /> Part of this process is research that looks into inhibitors for the MCU.

Uptake of calcium into the mitochondria is pivotal for signalling and bioenergetic processes, but overload of calcium causes release of [http://proteopedia.org/wiki/index.php/Cytochrome_c cytochrome c], overproduction of [https://en.wikipedia.org/wiki/Reactive_oxygen_species reactive oxygen species (ROS)], swelling of the mitochondria, and opening of the [https://en.wikipedia.org/wiki/Mitochondrial_permeability_transition_pore mitochondrial permeability transition pore (mPTP)] which all contribute to cell death. Therefore, the MCU has become a target of interest for therapies for certain conditions (like the ones above).<ref name="Woods" /> Part of this process is research that looks into inhibitors for the MCU.

Finding an good inhibitor of MCU is no small task. First of all, in the inhibitors that have already been discovered, there is no apparent structure-activity relationship that could predict their inhibitory activity. Additionally, many inhibitors of the MCU are not selective enough for the MCU or have other off-target effects that negatively affect the cell. Among the discovered inhibitors of the MCU are Mitoxantrone and DS16570511 with DS16570511 being the most potent. Furthermore, NecroX-5, KB-R7943, minocycline, and doxycycline have been shown to have inhibitory activity. However, all of these inhibitors are subject to the issues listed before.<ref name="Woods" />

Finding an good inhibitor of MCU is no small task. First of all, in the inhibitors that have already been discovered, there is no apparent structure-activity relationship that could predict their inhibitory activity. Additionally, many inhibitors of the MCU are not selective enough for the MCU or have other off-target effects that negatively affect the cell. Among the discovered inhibitors of the MCU are [https://en.wikipedia.org/wiki/Mitoxantrone Mitoxantrone] and DS16570511 with DS16570511 being the most potent. Furthermore, NecroX-5, KB-R7943, [https://en.wikipedia.org/wiki/Minocycline minocycline], and [https://en.wikipedia.org/wiki/Doxycycline doxycycline] have been shown to have inhibitory activity. However, all of these inhibitors are subject to the issues listed before.<ref name="Woods" />

ANTIBIOTIC STRUCTURES?

Inorganic salts and coordination complexes have also been shown to inhibit calcium uptake. Specifically, the trivalent lanthanide ions can competitively inhibit the uniporter because of their similar ionic radii and coordination preferences to calcium. In addition, several transition metal coordination complexes (most notably Co, Cr, and Rh) with amine ligands have been shown to inhibit calcium uptake. Again, there is no apparent structure-activity relationship that predicts this behavior.<ref name="Woods" />

Sandbox Reserved 1626: Difference between revisions

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@@ Line 47: / Line 47: @@
 == Regulation/Inhibition ==
-Uptake of calcium into the mitochondria is pivotal for signalling and bioenergetic processes, but overload of calcium causes release of cytochrome c, overproduction of reactive oxygen species (ROS), swelling of the mitochondria, and opening of the mitochondrial permeability transition pore (mPTP) which all contribute to cell death.  Therefore, the MCU has become a target of interest for therapies for certain conditions (like the ones above).<ref name="Woods" />  Part of this process is research that looks into inhibitors for the MCU.
+Uptake of calcium into the mitochondria is pivotal for signalling and bioenergetic processes, but overload of calcium causes release of [http://proteopedia.org/wiki/index.php/Cytochrome_c cytochrome c], overproduction of [https://en.wikipedia.org/wiki/Reactive_oxygen_species reactive oxygen species (ROS)], swelling of the mitochondria, and opening of the [https://en.wikipedia.org/wiki/Mitochondrial_permeability_transition_pore mitochondrial permeability transition pore (mPTP)] which all contribute to cell death.  Therefore, the MCU has become a target of interest for therapies for certain conditions (like the ones above).<ref name="Woods" />  Part of this process is research that looks into inhibitors for the MCU.
-Finding an good inhibitor of MCU is no small task.  First of all, in the inhibitors that have already been discovered, there is no apparent structure-activity relationship that could predict their inhibitory activity.  Additionally, many inhibitors of the MCU are not selective enough for the MCU or have other off-target effects that negatively affect the cell.  Among the discovered inhibitors of the MCU are Mitoxantrone and DS16570511 with DS16570511 being the most potent.  Furthermore, NecroX-5, KB-R7943, minocycline, and doxycycline have been shown to have inhibitory activity.  However, all of these inhibitors are subject to the issues listed before.<ref name="Woods" />
+Finding an good inhibitor of MCU is no small task.  First of all, in the inhibitors that have already been discovered, there is no apparent structure-activity relationship that could predict their inhibitory activity.  Additionally, many inhibitors of the MCU are not selective enough for the MCU or have other off-target effects that negatively affect the cell.  Among the discovered inhibitors of the MCU are [https://en.wikipedia.org/wiki/Mitoxantrone Mitoxantrone] and DS16570511 with DS16570511 being the most potent.  Furthermore, NecroX-5, KB-R7943, [https://en.wikipedia.org/wiki/Minocycline minocycline], and [https://en.wikipedia.org/wiki/Doxycycline doxycycline] have been shown to have inhibitory activity.  However, all of these inhibitors are subject to the issues listed before.<ref name="Woods" />
+ANTIBIOTIC STRUCTURES?
 Inorganic salts and coordination complexes have also been shown to inhibit calcium uptake.  Specifically, the trivalent lanthanide ions can competitively inhibit the uniporter because of their similar ionic radii and coordination preferences to calcium.  In addition, several transition metal coordination complexes (most notably Co, Cr, and Rh) with amine ligands have been shown to inhibit calcium uptake.  Again, there is no apparent structure-activity relationship that predicts this behavior.<ref name="Woods" />