In vitro ADME profiling

Included in this table are criteria related to kinase inhibition, including detailed analyses of reversibility, detergent effects, and competition with ATP. Also listed are criteria for selectivity, cellular activity, and the physicochemical and in vitro ADME profiles. The final two criteria require the lead to be part of a series of compounds with demonstrated SAR. 

In vitro ADME profile assay selection and profile... 

Figure 8. Heat map of a cluster of BioPrint compounds with similar in vitro ADME profiles. Eight ADME assays are clustered on the X-axis and 8 compounds are clustered on the Y-axis. Normalized data range from 0 (blue-green) to 2 (red). Clustering is performed using Pearson correlation and complete linkage using normalized dataset. Where available in literature, human in vivo oral absorption (oa) and oral bioavailability (ba) values (%) are presented after the compound name.

Figure 8 shows a cluster of BioPrint compounds with similar ADME profiles. All the compounds in this cluster share the pharmacokinetic properties of having near total oral absorption and oral bioavailability. Thus, we have identified an in vitro ADME profile that appears to be highly predictive of good absorption and bioavailability properties. 

Wu X, Wang J, Tan L et al (2012) In vitro ADME profiling using high-throughput rapid-fire mass spectrometry cytochrome p450 inhibition and metabolic stability assays. J Biomol Screen 17 761-772... 

In Vitro ADME Profiling and Pharmacokinetic Screening in Drug Discovery... 

Chapter 21 In Vitro ADME Profiling and Pharmacokinetic Screening in Drug Discovery Table 21.2. Pooling Strategies for Pharmacokinetic Evaluation of Drug Candidates... 

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