Single cell physicochemical properties

Poor intestinal absorption of a potential drug molecule can be related to poor physicochemical properties and/or poor membrane permeation. Poor membrane permeation could be due to low paracellular or transcellular permeability or the net result of efflux from transporter proteins including MDRl (P-gp) or MRP proteins situated in the intestinal membrane. Cell lines with only one single efflux transporter are currently engineered for in vitro permeability assays to get suitable data for reliable QSAR models. In addition, efforts to gain deeper insight into P-gp and ABC on a structural basis are going on [131, 132]. 

The PDQ method [21] is a partitioning scheme that is based on 3-point pharmacophores. In this scheme, each potential 3-point pharmacophore in a pharmacophore key is considered as a single cell. A molecule is mapped onto the key by identifying the 3-point pharmacophores that it contains. Thus, a molecule will typically occupy more than one cell this is in contrast to partitioning schemes based on physicochemical properties in which each molecule occupies a single cell. The pharmacophore keys for a set of molecules can be combined into an ensemble pharmacophore which is the union of the individual keys. The resulting ensemble key can be used to measure total pharmacophore coverage, to identify pharmacophores that are not represented in the set of molecules and to compare different sets of molecules. 

Diversity is typically measured using a distance-based or cell-based method cost is typically given as reactant cost/gm and physiochemical properties such as AMW are typically measured as the difference in the distribution of the property in the library compared to the distribution of the same property in a collection of known drugs. The weights, wl5 w2j w3> are user-defined and are typically set so that diversity is maximized, while the cost and physicochemical properties are minimized. This weighted-sum approach leads to a single solution that represents one particular compromise in the objectives. Several other groups have also adopted this approach [67, 71 73]. 

The single characteristic that encompasses phenomena at all scales and in all fuel cell components is the fuel cell polarization curve. The polarization curve of a membrane-electrode assembly (MEA), a single cell, or a fuel cell stack furnishes the link between microscopic structure and physicochemical properties of distinct cell components on the one hand and macroscopic cell engineering on the other. It thus condenses an exuberant number of parameters, which lies in the 50s to 100s, into a single response function. Analysis of parametric dependencies in the polariz-tion curve could be extremely powerful at the same time, it could as well be highly misleading if applied blindly. ... 

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