Thioridazine, the most potent phenothiazine in tumor regulation, is well-known to cause genotoxicity, QT prolongation and life-threatening cardiac arrhythmias through its interaction with DNA and inhibition of several cardiac ion channels r4espectively. Thioridazine, and similar drugs in its chemical class, remain laboratory curiosities that have not been able to secure FDA approval. Oncorx pharmaceuticals has developed a first-in-class family of phenothiazine drugs that interact minimally with DNA, hERG K+ channels, Na+K+-ATPase channels and are low risk for toxixites caused by these interactions.
Oncorx Pharmaceuticals has additionally identified a previously un-recognized cause of life-threatening cardiotoxicities involving the generation of highly reactive oxygen (ROS) phenothiazine metabolites that are responsible for their genotoxicity, QT prolongation, cardiac arrhythmias and torsade de pointes. These metabolites are formed by the biotransformation of the parent phenothiazine to highly reactive quinonimines through enzymatic conversion by myeloperoxidases in the patient's blood. Oncorx Pharmaceuticals has developed the first family of phenothiazine drugs that block the formation of these highly reactive oxygen metabolites.
Cancer patients, unlike the general population, have a marked elevation of myeloperoxidase in their blood, making them a high-risk population for life-threatening cardiotoxicities involving the generation of highly reactive oxygen (ROS) .