Analysis of Attrited Compounds

An analysis of more than 130 preclinical candidates that had attrited during further development showed the failure of the chemotype approach (i.e. that a compound of the same/similar chemotype will have similar risks of attrition and that a structurally diverse chemotype will offer the best approach to minimize attrition risk) and 2D structure-based methods to be able to effectively differentiate compounds [29]. Thus, the risk of failing or succeeding in development is not related to being of the same chemotype , and differentiation by this method may not be the most effective way dangers are both that a valuable series/chemotype could be discarded because of one bad result and that a structurally different compound may actually have similar off-target effects (e.g. due to the decoration versus the scaffold). 

CYP3A4 inhibition issue purple, toxicity issue). 

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Collaborators have profiled their own compounds in the identical assays, to produce enhanced proprietary data sets. These are generally project and attrited compounds. Examples of results using data from these compounds in the context of BioPrint compounds are given in Section 2.3.2.1 for the differentiation ofhits/leads and in Section 2.3.2.2 for the analysis of attrited compounds. 

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