Interaction Fields in ADME and Safety

Einally, there is a fourth program which encapsulates GRIND descriptors named ALMOND. ALMOND theory is described in Chapter 6. What we will describe below refers to our involvement in utilizing the GRIND descriptors to model and understand various ADME and safety properties. 

Accordingly, we will briefly outline the use of MIEs in three research areas. In absorption, the use of MIEs to understand and model permeability through PAMPA, Caco-2, MDCK cells as well as BBMEC cells has been demonstrated. However, this approach is limited to a passive mechanism. 

Outliers in these models, as well in biological assays, are due to several reasons which encompass issues related to transporters in the cells which could be efflux or uptake transporters. We have tried to address the problem using MI Fs to understand P-glycoprotein (PGP) efflux, especially as it pertains to substrates. 

Secondly, we will describe the use of GRIND descriptors to obtain a general model for inhibition of the K channel in the heart, known as the Human Ether-a-go-go Gene (HERG). 

Finally MIFs will be used to explain cytochrome P450 (CYP) 3A4 inhibition. The use of METASITE in understanding and predicting the site of metabolism 

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I 9 Molecular Interaction Fields in ADME and Safety 9.3.1.3 ALMOND Descriptors... 

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