Despite the increase in global biology and chemistry knowledge the discovery of effective and safe new drugs seems to become harder rather than easier. Some of this challenge is due to increasing demands for safety and novelty, but some of the risk involved in this should be controllable if we had more effectively learnt from our failures. This perspective reflects on some of the learnings of recent years in relation to the causes of attrition. The term Molecular Obesity is introduced to describe our tendency to build potency into molecules by the inappropriate use of lipophilicity which leads to the premature demise of drug candidates.
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