Drug design anticancer agents

Strobel et al. (101) reported a unique approach to delivery of anticancer agents from lactide/glycolide polymers. The concept is based on the combination of misonidazole or adriamycin-releasing devices with radiation therapy or hyperthermia. Prototype devices consisted of orthodontic wire or sutures dip-coated with drug and polymeric excipient. The device was designed to be inserted through a catheter directly into a brain tumor. In vitro release studies showed the expected first-order release kinetics on the monolithic devices. 

In reviewing intraarterial infusion of microencapsulated anticancer agents and its clinical applications, Nemoto (124) concluded that this mode of treatment can be used for a wide variety of tumors, providing remarkable therapeutic effects with minimal systemic toxicity. However, 25% of the treated tumors failed to respond, which was thought to be attributable to either inadequate catheterization, inadequate dose relative to tumor size, insufficient tumor vascularity, low drug sensitivity, or a combination of these factors. More carefully designed studies will be necessary before this technique is likely to meet with widespread acceptance. 

Ion transfer, 14 (1977) 1 Irinotecan, anticancer agent, 34 (1997) 68 Isothermal titration calorimetry, in drug design, 38 (2001) 309... 

In our group, a major part of our research is devoted to the design of new anticancer drugs. Our recent efforts towards the discovery of new platinum-, ruthenium- and osmium-based anticancer agents provide the topic for this account and a section is devoted to each metal. We focus on recent results from our lab in the context of other developments and related research in this field (hence our coverage of the field is focused on these areas and is not comprehensive). 

The overexpression of GSTs in some cancer cells, particularly of GST Pl-1, offers an opportunity to detect and treat some cancer types (e.g., ovarian cancer). Recent developments in the design of small molecules that either inhibit the catalytic activity of GST Pl-1 or use GST Pl-1 catalytic site to release the actual anticancer agent, have shown promising results in preclinical studies, with the graduation of 66 and 96 as potential anticancer drug candidates currently undergoing clinical trials. 

Rowinsky EK. The pursuit of optimal outcomes in cancer therapy in a new age of rationally designed target-based anticancer agents. Drugs 2000 60 1-14 discussion 41 —42. 

Topoisomerase Interactive Drugs. Topoisomerases I and II have emerged as interesting targets for the design of new anticancer agents (Table 4),... 

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