Canfosfamide Hydrochloride

The potential fates in indirect potable reuse systems of 2179 pharmaceutical compounds that currently have been used or may be introduced within the next five years were estimated using a modified quantitative structure activity relationship model. Over 90% of the pharmaceutical compounds analyzed were estimated in this study as non-persistent in indirect potable reuse systems where the final removal barrier was sub-surface transport. The removal mechanisms of biodegradation and sorption were considered in assessing their persistence. The percentage of compounds produced by biotechnology was expected to increase from less than 20% to greater than 60% in the near future and this should result in a trend of decreasing persistence for future compounds. The potential rejection in indirect potable reuse systems that use reverse osmosis (RO) as the primary barrier was statistically evaluated. In order to evaluate RO performance, a multiple linear regression analysis was done using SPSS (ver. 17) and the main rejection mechanism for low molecular weight compounds was electrostatic repulsion. Treatment by RO is capable of removing greater than 95% of future compounds and would be expected to perform as efficiently as with currently used compounds.

The vulnerability of some cancer cells to oxidative signals is a therapeutic target for the rational design of new anticancer agents. In addition to their well characterized effects on cell division, many cytotoxic anticancer agents can induce oxidative stress by modulating levels of reactive oxygen species (ROS) such as the superoxide anion radical, hydrogen peroxide and hydroxyl radicals. Tumour cells are particularly sensitive to oxidative stress as they typically have persistently higher levels of ROS than normal cells due to the dysregulation of redox balance that develops in cancer cells in response to increased intracellular production of ROS or depletion of antioxidant proteins. In addition, excess ROS levels potentially contribute to oncogenesis by the mediation of oxidative DNA damage. There are several anticancer agents in development that target cellular redox regulation. The overall cellular redox state is regulated by three systems that modulate cellular redox status by counteracting free radicals and ROS, or by reversing the formation of disulfides; two of these are dependent on glutathione and the third on thioredoxin. Drugs targeting S-glutathionylation have direct anticancer effects via cell signalling pathways and inhibition of DNA repair, and have an impact on a wide range of signalling pathways. Of these agents, NOV-002 and canfosfamide have been assessed in phase III trials, while a number of others are undergoing evaluation in early phase clinical trials. Alternatively, agents including PX-12, dimesna and motexafin gadolinium are being developed to target thioredoxin, which is overexpressed in many human tumours, and this overexpression is associated with aggressive tumour growth and poorer clinical outcomes. Finally, arsenic derivatives have demonstrated antitumour activity including antiproliferative and apoptogenic effects on cancer cells by pro-oxidant mechanisms, and the induction of high levels of oxidative stress and apoptosis by an as yet undefined mechanism. In this article we review anticancer drugs currently in development that target cellular redox activity to treat cancer.