Therapeutic targets, drug development

At the health care provider level, choices will be made among many therapeutic regimens that differ in effectiveness and cost. At the producer level, pharmaceutical companies must decide whether targeted drug development is economically feasible. Will there be a sufficient return on investment to justify the risks involved in pharmacogenomic research Will companies only pursue research and drug development for diseases for which there is... 

All PKG substrates identified so far in human platelets interact directly or indirectly with the actin filament and the cytoskeleton of the cell and are involved in the negative regulation of platelet activation after phosphorylation by PKG. The proteomic approach in combination with functional studies is a very successful tool for studying phosphorylation-dependent effects in platelets. Ongoing proteome studies will now focus on membrane proteins for new therapeutic targets to develop antithrombotic drugs. 

The exact role of individual histone acetylations will have to be determined in the context of other modifications and the number of lysine residues effected. However, the general importance of histone acetylation as a regulator for chromatin activity is undisputed. This leads to the intriguing possibility to develop drugs that target histone acetylation for therapeutic purposes. The primary targets for drug development are the histone acetyl transferases (HATs) and the histone deacetylases (HDACs) which introduce and remove histone acetylations [2, 3]. 

The concept of drug development is based on the findings that retinoid receptors (RARs and RXRs) offer a new approach by targeting different genes depending on the activated retinoid receptor complexes. The multiplicity of these retinoid signaling pathways affords potential for therapeutic opportunity as well as retinoid therapy associated undesired side effects. It is possible that the indiscriminate activation of all pathways by nonspecific retinoid ligands could lead to unacceptable side effects so that any enhanced efficacy would be obtained at the cost of enhanced toxicity. 

Polosa R, Holgate ST Adenosine receptors as promising therapeutic targets for drug development in chronic airway inflammation. Curr Drug Targets... 

As members of the GPCR superfamily have historically dominated drug development programs, so too has interest in chemokine receptors as therapeutic targets. 

Overall, the prodrug approach is a well-established strategy to improve the bioavailability and targeting of pharmacophores, and is a vital component in the development of therapeutics and drug-delivery strategies. 

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. 

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