Finding New Chemical Tools and Leads

Interestingly, given the discussion of the importance of understanding small molecule-target protein interactions early in drug discovery, there is renewed interest in reexamining many older drugs to more fully understand how they work [10]. 

Biological effect Protein target Natural product Reference 

Immunosuppressive, anti cancer Microtubule binder/ stabilizer OH = = OH = OH Ov NH2 i T OH O discodermolide 59 

Increasing information-better decisions-fewer compounds needed 

Peter Schultz s team used a combinatorial library of purines to identify agents that could disassemble multinucleated myotubes into mononucleated fragments (a morphological differentiation screen). A new microtubule-binding molecule, mysoseverin, was identified in this way [19]. 

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DNA flow cytometry is a very useful tool that permits rapid, objective assessment of a large number of cells but may not be readily available. Comet assay, when combined with centrifugal elutriation, can provide a useful in vitro model to study differences in metabolism and the susceptibility of different te,sticular cell types to DNA-damaging compounds. Thus, new findings using these systems should lead to greater knowledge about why a chemical or class of chemicals can cause testicular toxicity. 

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