SOSA, Selective optimization of side activities

In theory, a drug with poor target specificity can be modified to enhance the side effect and decrease the original effect. This process is called selective optimization of side activities (SOSA). A significant advantage to SOSA is that the molecules, now considered hits for their secondary activity, have already been studied in clinical trials. The oral... 

The SOSA approach (SOSA = Selective Optimization of Side Activities) represents an original alternative to high-throughput screening (HTS) [29-31]. SOSA consists of two steps ... 

A new strategy in drug discovery, the selective optimization of side activities (the SOSA approach), has been formulated by Camille Wermuth [17,18 cf. Chapter I—1], In this approach, minor side activities of active compounds serve as the starting point for structural variations, ultimately to obtain analogues that now have the former side effect as their main activity. In this manner, nanomolar acetylcholinesterase (AChE) inhibitors as well as nanomolar muscarinic M, receptor and 5-HT3 receptor ligands could be derived from the antidepressant minaprine [17,18],... 

Wermuth, C. G. Selective optimization of side activities the SOSA approach. Drug Discov. Today 2006, 11, 160-164. 

Besides the presented methods there are a lot of other ways to generate hits in pharmaceutical industry. Methods like SOSA (selective optimization of side activities) [16] and fragment-based approaches are presented in other chapters and are therefore not discussed here. We have tried to provide an overview of the most often used - at least from our viewpoint - lead generation method in this chapter. It is the authors experience that no single lead generation method... 

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