ADME-Tox

The partition coefficient and aqueous solubility are properties important for the study of the adsorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) of drugs. The prediction of the ADME-Tox properties of drug candidates has recently attracted much interest because these properties account for the failure of about 60 % of all drug candidates in the clinical phases. The prediction of these properties in an early phase of the drug development process could therefore lead to significant savings in research and development costs. 

Ekins S, Boulanger B, Swaan PW, Hupcey MAZ. Towards a new age of virtual ADME/TOX and multidimensional drug discovery. J Comput Aided Mol Des 2002 16 381-401. 

Ekins S. Systems-ADME/Tox Resources and network approaches. J Pharmacol Toxicol Methods 2006 53 38-66. 

The Basic Concept of the QSAR Technique. The QSAR technique has been widely employed in modeling biological activities as well as ADME/Tox (absorption, distribution, metabolism, excretion, toxicity) properties. This approach was first introduced by Flansch et al. in 1963, on the basis of linear... 

Poor pharmacokinetics and toxicity are important causes of costly late-stage failures in drug development. It is generally recognized that, in addition to optimized potency and specificity, chemical libraries should also possess favorable ADME/Tox and druglike properties [77-80]. Assessment of druglike character is an attempt to decipher molecular features that are likely to lead to a successful in vivo and, ultimately, clinical candidate [81-83]. Many of these properties can be predicted before molecules are synthesized, purchased, or even tested in order to improve overall lead and library quality. 

To date, many of the reported ADME/Tox models have been rule based. For example, some research groups have used relatively simple filters like the rule of 5 [93] and others [94] to limit the types of molecules evaluated with in silico methods and to focus libraries for HTS. However, being designed as rapid computational alert tools aimed at a single property of interest, they cannot offer a comprehensive picture when it comes to understanding ADME properties. 

Good secondary screens for ADME/Tox and selectivity. It used to be these were too expensive to consider at medium throughput, but this is... 

MetaDrug Metabolism database. Metabolite prediction. Metabolite prioritization, QSAR models for enzymes, transporters and network building algorithms for Systems-ADME/Tox www.genego.com... 

A new tool for computational ADME/Tox called MetaDrug includes a manually annotated Oracle database of human drug metabolism information including xenobiotic reactions, enzyme substrates, and enzyme inhibitors with kinetic data. The MetaDrug database has been used to predict some of the major metabolic pathways and identify the involvement of P450s [78]. This database has enabled the generation of over 80 key metabolic... 

There have been considerable efforts toward modeling ADME/Tox properties and the biophysical properties of molecules (see chapters 18-20, 22, 28), including numerous commercial software solutions. Simulations Plus (http //www.simulations-plus.com/) have developed GastroPlus, a product... 

Sugano, H. Artifidal membrane technologies to assess transfer and permeation of drugs in drug discovery. In ADME/Tox Approaches, Tests, B.,... 

Avdeef, A., Voloboy, D., Foreman, A. Dissolution-solubility of multiprotic drugs pH, buffer, salt, dual-solid, and aggregation effects. In ADME/Tox Approaches, Van de Waterbeemd, H ... 

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