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Data from MS/MS studies was used in the structural identification of all metabolites.
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Full details for all biological assays can be found in Ref. 2 or references cited therein.
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This whole blood assay was used in many p38α programmes to compare in-vitro potency against potency in a cellular system in a whole blood medium which takes into account other factors such as cell permeability (not likely to be a significant problem for the majority of compounds in this article as assessed by Caco-2 permeability experiments) and off-target binding including plasma protein binding. In regard to the latter factor, recent opinion would suggest that extreme caution should be taken when prioritizing compounds based on results from in-vitro assays which are adversely affected by the inclusion of plasma proteins because unbound plasma concentrations in-vivo are determined not by plasma protein binding but by intrinsic clearance after oral dosing. For further discussion see
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This whole blood assay was used in many p38α programmes to compare in-vitro potency against potency in a cellular system in a whole blood medium which takes into account other factors such as cell permeability (not likely to be a significant problem for the majority of compounds in this article as assessed by Caco-2 permeability experiments) and off-target binding including plasma protein binding. In regard to the latter factor, recent opinion would suggest that extreme caution should be taken when prioritizing compounds based on results from in-vitro assays which are adversely affected by the inclusion of plasma proteins because unbound plasma concentrations in-vivo are determined not by plasma protein binding but by intrinsic clearance after oral dosing. For further discussion see: X. Liu, C. Chen, and C.E.C.A. Hop Curr. Top. Med. Chem. 11 2011 450
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