Our work led to the identification of preclinical candidate VU0424238 (10) (Figure 3).22 In a 28-daytoxicology study, a NHP species-specific aldehyde oxidase (AO) metaboliteaccumulated after 14 days, resulting in pronounced anemia (nonmechanismbased); therefore, further development of 10 was halted.Detailed metabolic studies has shown that in NHPs, the pyrimidineheadgroup is oxidized by AO, whereas, in rats, this oxidation processis carried out by xanthine oxidase (XO).23 Thus, these observed AO/XO metabolism differences between speciesmay be linked to the observed NHP-specific toxicity. This evidence concerns the gene XDH and anemia (phenotype).