SOSA approach

The SOSA approach can be enhanced by virtual screening methods which use reference compound sets and molecular descriptors together with advanced chemoinformatics methods to compare and rank the similarity of considered candidate molecules. 

New Leads from Old Drugs The SOSA Approach 1.3.3.1 Definition... 

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 ... 

Fig. 1.16 A successful SOSA approach allowed the identification of the antibacterial sulfonamide sulfathiazole as a ligand of the endothelin ETfl receptor and its optimization to the selective and potent compounds BMS-182874, BMS-193884, and BMS-207940 [34,35],...

During years of practicing SOSA approaches, it has been observed at Prestwick that, starting with a drug molecule as a lead substance in performing analogue... 

As mentioned above, a differentiating peculiarity of this type of library is that it is constituted by compounds that have already been safely given to humans. Thus, if a compound were to hif with sufficient potency on an orphan target, there is a high chance that it could rapidly be tested in patients for Proof of Principle. This possibility represents another advantage of the SOSA approach. 

The design of analogues of the second category is sometimes fortuitous, as the result of a pharmacological or a clinical feed-back. For these structural analogues , the observation of a new activity can also result from a planned and systematic investigation such as provided by the use of the PASS program or the SOSA approach. 

Wermuth CG. The SOSA approach an alternative to high-throughput screening. Med. Chem. Res., 2001, 10, 431—439. 

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. 

II. FIRST STRATEGY ANALOG the SOSA approach B. Inhibitors of the ACE... 

Among them, a typical illustration of the SOSA approach is shown by the development of a selective ligand for the endotheline ETa receptors by scientists from Bristol-Myers-Squibb. " Starting from an in-house library, the antibacterial compound sulfathiazole (Fig. 5.13) was an initial, but weak, hit (IC50 = 69 p,M). Testing of related sulfonamides identified the more potent sulfisoxazole (IC50 = 0.78 xM). Systematic variations led finally to the potent and selective... 

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