Both, gene enrichment analysis of predicted targets and previous studies of target validation, support the involvement of these miRNAs in several biological processes and age‐related diseases.
To ensure rational targeted therapy, target validation of compounds should be carried out with multiple reliable and unbiased methods.
Proximal tubule candidate anchor genes/probesets were further filtered to those with a minimum of 10 fold-change difference to reduce the number of targets for validation.
In our previously published list of 186 p63 targets the percentage of validation was almost complete, suggesting that additional relevant targets were below the stringent threshold.
The relatively high proportion of target validation failures could be due to erroneous target predictions, low-abundance targets or miRNA-guided cleavage products, or low-abundance miRNAs with limited or no activity.
While in vivo murine tumor models evaluating the efficacy of statins have been employed, differences in drug metabolism between species and lack of target validation in many studies suggests the potential of off target effects playing a role in statin response [43], [44], [45].
As an example of target validation, reversible, systemic expression of a dominant-negative mutant Myc oncogene in transgenic Ras-induced lung carcinoma model caused the tumours to regress, whereas effects on normal regenerating tissue were well tolerated and reversible (Soucek et al, 2008).
Although in the last 10 years significant progress has been made in the identification and classification of oncogenic lesions that mark potential therapeutic targets, validation of these targets using pharmacological tools has suffered from an incomplete understanding of what represents meaningful target inactivation.
All the characteristics of the models and clinical patient history are being loaded into an internal database for efficient use in terms of target validation, biomarker discovery, and preclinical evaluation of new agents.
The concepts of target validation in drug design and the concepts of drug delivery are discussed.
