These in vitro ADME and physicochemical property criteria, together with previously described potency criteria (Bmax/Kd > 10), should be considered for lead prioritization and rational ligand design.
Meristematic cells in the shoot apex of angiosperms would qualify as stem cells, using this bi-potency criterion, but multicellular slime molds and Volvox would not contain such stem cells (see Appendix 1).
I find it especially useful that the authors share their preferred definitions and settings in terms of applied similarity criteria, potency difference criteria, as well as activity measurements, thus highlighting scope and limitations of the underlying methodology.
(b) Potency difference criterion: At least two orders of magnitude.
(b) Potency difference criterion: At least two orders of magnitude (≥ 100-fold).
(iv) A potency difference criterion must be established (i.e., when is a potency difference considered to be large?).
In addition, setting the potency difference criterion for meaningful activity cliff and SAR analysis is subject to heuristic approximations.
However, if inactive compounds are taken into consideration, a potency difference criterion is no longer applicable to define activity cliffs.
To clearly establish the potency difference criterion, it must not only be decided how large a potency difference between two compounds should be but also considered which type of potency measurements should be utilized.
The assessment of activity cliffs requires clearly defined similarity and potency difference criteria.
For a meaningful assessment of activity cliffs, similarity and potency difference criteria need to be clearly defined.
