ADME Applications

A thorough review, even with a very superflcial mention of the vast literature on ADME, QSPR and QSAR applications involving the use of lipophilicity, would be a daunting task and it is far beyond the scope of this chapter. However, it is no surprise that three international conferences, in recent years, have been specifically dedicated to this topic, and that the development of newer and faster screening methods, in some cases seeking to produce alternative lipophilicity parameters to the classical or nonclassical log Pod determinations are still an active area of interest [6]. 

We also note, in closing, that lipophilicity is a key parameter of the well-known Rule-of-5 [19] and it represents probably the single most broadly used parameter in these efforts whether the approach is experimental or in silica [20]. 

The continuing quest for novel and safer drugs has led to the introduction of myriad new technologies within the pharmaceutical industry. Notably, advances in genomics, high-throughput screening, combinatorial chemistry. 

Early Access to physicochemical and in vitro ADME Data 

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Completed by CAF Initiator - Thia ronrt should be used witlt proceduie PSM-ADM-11, Management of Change Applicable Cost Codes for Affected Equipment/Area ... 

These properties have had a significant impact on modifications of iterative methods and provide the possibility of applications of the two-parameter iterative ADM ... 

Kesurn GM, Molnar L. METAPRINT a metabolic fingerprint. Application to cassette design for high-thronghpnt ADME screening. J Chem Inf Comput Sci 2002 42 437-44. 

From a methodological viewpoint, our results suggest that range and sensitivity are useful descriptors of property spaces and can parameterize the capacity of a given molecule to span broad conformational and property spaces. In other words, range and sensitivity appear as promising descriptors of the dynamic behavior of a molecule. Their application to other dynamic QSAR studies [in particular, absorphon, distribution, metabolism and excretion (ADME) behavior] is under investigahon. 

Goodford, P. J. The basic principles of GRID. In Molecular Interaction Fields Application in Drug Discovery and ADME Prediction (Methods and Principles in Medicinal Chemistry), Cruciani, G., Mannhold, R. Kubinyi, H., Folkers, G. 

Goodford P (2006) In Cruciani G, Mannhold R, Kubinyi H, Folkers G (eds) Molecular interaction fields applications in drug discovery and ADME prediction. Wiley, New York, p 3... 

In the following section, the calculation of the VolSurf parameters from GRID interaction energies will be explained and the physico-chemical relevance of these novel descriptors demonstrated by correlation with measured absorption/ distribution/metabolism/elimination (ADME) properties. The applications will be shown by correlating 3D molecular structures with Caco-2 cell permeabilities, thermodynamic solubilities and metabolic stabilities. Special emphasis will be placed on interpretation of the models by multivariate statistics, because a rational design to improve molecular properties is critically dependent on an understanding of how molecular features influence physico-chemical and ADME properties. 

LGMS APPLICATION IN HIGH-THROUGHPUT ADME SCREEN... 

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