Therapeutic target classes

Table 1. Therapeutic target classes of current drugs (Drews, 2000).

A major challenge to the development of new drugs is the discovery of new therapeutic targets. For example, the phenomenal success of fluoxetine (Prozac ) has been due to the fact that it was the first selective serotonin re-uptake inhibitor approved for world market release, combined with its improved adverse drug reaction profile. However, no new classes of antidepressants have emerged in recent years. 

Three families of serotonin receptor, the 5-HT family, the 5-HT2 family and the family that includes the 5-HT4, 5-ht6 and 5-HT7 receptors represent the three major classes of 5-HT receptor that are G-protein-coupled receptors (Ch. 19). The 5-HT3 receptor is a ligand-gated ion channel and is a separate family. Although each serotonin receptor can be potently activated by 5-HT, differences insignal transduction mechanisms,neuroanatomical distribution and affinities for synthetic chemicals create opportunities for drug discovery and make each 5-HT receptor subtype a potential therapeutic target. 

Robertson, J. G. (2007). Enzymes as a special class of therapeutic target clinical drugs and modes of action. Current Opinion in Structural Biology 17, 674—679. 

Methods and approaches that can simultaneously determine mixtures of drug candidates provide a powerful way to select an optimal drug candidate within a specific therapeutic area or a targeted class of compounds. Using relatively simple isolation and chromatography conditions, LC/MS/MS approaches are an effective way to evaluate new lead compounds for subsequent development. Consequently,... 

Human rhino viruses (HRVs) are the single most significant causative agents of the common cold. HRV 3C-protease, a cysteine protease, plays a critical role in the replication cycle of HRVs and thus constitutes a potential therapeutic target for the control of HRVs and common cold. Singh et al established the structure-activity relationships of various naphthoquinones as HRV 3C-proteasa inhibitors and compared the activities of ortho- versus -para- quinones. The results indicated that the mode of action of the two classes of compounds is different [207]. 

In this discussion of Kvl. 5 selectivity, it is worth mentioning that a large variety of compounds, outside of discovery efforts explicitly focusing on Kvl.5 as a therapeutic target, have been found to inhibit Kvl.5. Not only a large number of antiarrhythmic agents, but also many compounds developed for therapeutic classes other than ion channels have been reported to inhibit the channel, in many instances at their therapeutic concentrations [34]. 

GPCRs modulate a wide range of physiological processes and are implicated in numerous diseases. Therefore they form the largest class of therapeutic targets. G-protein coupled receptors represent the primary mechanism by which cells feel external environment and different stimuli, and pass the information to the interior of the cell. Abnormalities (usually by mutations but also by risk factors) of delicate balance in signaling mechanism often go to diseases and disorders, e.g. hypertension, hypertrophy, inflammatory diseases, cancer, fibrosis, diabetes, and diseases of central nervous system like Alzheimer disease. 

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