Triggers for Hematotoxicity Testing

There is a high prevalence of bone marrow toxicity with antiproliferative oncology compounds that also occurs with many non-antiproliferative compound classes but at a much lower prevalence. It is these non-antiproliferative compounds that are of greatest 

Rest ofthe sample was stained using the method by Saad et at. [59]. There are two non-nucleated erythroid populations based on LDS751 staining (LDS751 and LDS75T ). Additional stains (results not shown) indicate the LDS751 cells are reticulocytes and the LDS751 cells are mature non-nucleated erythrocytes. 

The first consists of selecting a handful of representative compounds ivhich cover the chemical space of a series and testing only those. If there are some alerts, then further compounds can be tested. This can be done systematically for all series of all projects. However, this absorbs a fair amount of resources for a potentially limited return on investment. 

The second approach necessitates a mechanism to identify compounds or chemical series from a project that enter the screening cascade. These triggers may include target-related information, previous experience and in silica analysis of compounds. 

One of the roles of a toxicologist involved in early discovery as a project team representative can be to generate a list of potential and likely toxicities deduced from target-related information such as tissue expression, similarity to other targets, precedent described in literature and sometimes chemical structure similarity. When 

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