In 1997, Drews and Ryser summarized what they termed classic drug targets.448 These targets of marketed drugs were broken down into 11 classes comprising about 500 targets (Table 23). Receptor targets dominated these numbers, being twice as common for marketed drugs as enzyme targets, followed by factors and hormones, channels or unknown targets, and nucleic acid targets. Central nervous system (CNS) and related targets were the most common.
How have we done in various therapeutic and target areas? First, let us consider cancer. Modern chemotherapy started with nitrogen mustards in the 1940s. The NCI began systematic screening for new anticancer drugs in the 1950s. Chemotherapy following surgical removal of cancers was demonstrated to improve cure rates in the 1960s. Major drugs like cisplatin and paclitaxel were approved in the 1970s and 1990s. The tyrosine kinase inhibitor, imatinib, was approved in 2001 by the FDA, representing a new target-based paradigm in the field. Clearly a lot of progress has been made - but also clearly there is a long way to go to achieve the National Cancer Institute's goals.449 If you are diagnosed with a serious cancer today, and a cure is discovered for this cancer today, you will probably still die of this cancer because it takes so long to develop new drugs, even for cancer. The war on cancer is thus far from won, but the NCI has stated as its goal to eliminate suffering and death from cancer by 2015.450
Moving beyond cancer, new targets in the 1980s included phosphodiesterases (PDE). Who could have predicted that PDE inhibitors, which were studied extensively in the 1980s for heart failure (e.g., inhibitors of type 3 cAMP PDE, like amrinone),451 and later as antidepressants (e.g., rolipram),452 would ultimately yield billion dollar products for erectile dysfunction (e.g., inhibitors of type 5 cGMP PDE, such as sildenafil (Viagra)). This shift in emphasis raises other questions, though. A society that shifts its attention to ''desires rather than diseases'' is a society gone off track.455
The history of calcium antagonists provides an interesting case study in the development of a whole new therapeutic paradigm, one which continues to evolve as new compounds, new targets, and new medical uses are developed. Compounds such as verapamil, nifedipine, and diltiazem showed how widely divergent chemicals could all target similar ion channels (Figure 69).456 Ion channels continue to be of great interest as drug targets, beyond traditional therapy for hypertension, anesthesia, anxiety, epilepsy, and insomnia, as new opportunities are uncovered for this well-established therapeutic class in pain, autoimmune disease, cancer, and other areas.457
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