YT-001 acts by PREVENTING formation of damaging oxygen free radicals

The re-introduction of oxygen to ischemic tissue (whether in the setting of a heart attack or organ transplantation) can result in what is known as Reperfusion Injury.  The bulk of this Reperfusion Injury results from the generation of reactive oxygen species including oxygen free radicals.  The above scheme illustrates the major pathway associated with the generation of oxygen free radicals that underlie Reperfusion Injury.  Reperfusion is known to activate Protein Kinase C epsilon (PKCe) - one of the major gate keepers for the generation of oxygen free radicals. YT-001 is a PKCe inhibitor and thereby prevents (i) activation of cytokine receptors, (ii) changes in the mitochondria and (iii) uncoupling of eNOS both of which are sources of oxygen free radical generation.  Previous failed attempts to inhibit Reperfusion Injury were designed to "mop-up" oxygen free radicals AFTER they are generated and have initiated cell damage.  YT-001 acts by inhibitibing formation of oxygen free radicals BEFORE they are generated and have had a chance to initiate cell damage.

The above figures summarize finding with YT-001 in male Yorkshire pigs. 

The bar graph on the left shows data from two groups of animals - Control (blue) and YT-001 treated (red).  Baseline ejection fractions (measure of cardiac function) were similar in both groups prior to clamping the coronary artery (ischemia).  Heart function fell significantly in both groups (middle) after ischemia.  At the time of reperfusion the animals in the red group were given YT-001.  Following 3 hours of reperfusion (right) the YT-001 treated group had a significant improvement in cardiac function verses control (blue)

The bar graph on the right shows the amount of damage at the end of the experiment in both groups.  The YT-001 treated animals (red) had a 70% reduction in the size of the area of heart damage verses control (blue) animals.  These data can be found in the following manuscript.

Tetrahydrobiopterin (BH4) is an essential co-factor in the conversion of L-arginine to nitric oxide (NO).  It the setting of oxidative stress, BH4 is oxidized to dihydrobiopterin (BH2) and super oxide (SO) is generated instead of NO leading to inflammation.  The video below shows a rat mesenteric artery under intravital microscopy in the presence of 100 µM BH2.  You can see leukocytes sticking to the endothelium as a result of the BH2-induced inflammation.

The following video is recorded after 2 hours of exposure to BH2 and 10 µM YT-001.  There is no evidence cell sticking to the endothelium suggesting YT-001 blocks the damaging inflammation caused by oxidative stress (BH2) and SO generation.