Current Drug Metabolism - Volume 11, Issue 4, 2010

Many authors have been used Graph and Complex Network theory to approach very large metabolic networks with low computational cost. These large networks are graphical representations of real metabolic systems with essentially two components nodes and links. Nodes (represented by dots) are usually metabolites, enzymes, substrates, intermediary substances, metabolic reactions or transition states. Node-to-node link Read More

The integration of early ADMET (absorption, distribution, metabolism, excretion and toxicity) profiling, or simply prediction, of 'lead' molecules to speed-up the 'lead' selection further for phase-I trial without losing large amount of revenue. The ADMET profiling and prediction is mostly dependent of a number of molecular descriptors, for example, Lipinski's 'Rule of 5' (Ro5). Recently a large number of articles have been Read More

PF-02341066 is a selective c-Met/Alk tyrosine kinase inhibitor currently in clinical development as an anticancer agent. Non-clinical toxicokinetic evaluation in rats revealed gender-related differences in pharmacokinetics with at least 2-fold higher PF-02341066 plasma concentrations in males than females when administered the same dose. In general, lower systemic exposure of drugs that undergoes oxidative metabolism in Read More

Efficient drugs such as statins or mevinic acids are inhibitors of the rate-limiting enzyme of cholesterol biosynthesis, 3- hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGR), an enzyme responsible for the double reduction of 3-hydroxy-3-methyl-glutaryl coenzyme A. These compounds promoted the synthesis and evaluation of new inhibitors for HMGR, named HMGRIs. The high number of possible candidates creates the Read More

Complexity of metabolic systems can be undertaken at different scales (metabolites, metabolic pathways, metabolic network map, biological population) and under different aspects (structural, functional, evolutive). To analyse such a complexity, metabolic systems need to be decomposed into different components according to different concepts. Four concepts are presented here consisting in considering metabolic system Read More

The cytochrome P450 family is a large and diverse group of hemoproteins that are located in virtually all types of organism, such as bacteria, eukaryotes and even Archaea. These proteins are found throughout the body, however the highest concentrations are associated with liver. As the Human Genome Project completed, there are 57 genes and more than 59 pseudogenes divided among 18 families of CYP genes and 43 Read More

Colorectal cancer is one of the most frequent types of cancer in the world and generates important social impact. The understanding of the specific metabolism of this disease and the transformations of the specific drugs will allow finding effective prevention, diagnosis and treatment of the colorectal cancer. All the terms that describe the drug metabolism contribute to the construction of ontology in order to help scientists t Read More

Using graphic rules to deal with kinetic systems is an elegant approach by combining the graph representation (schematic representation) and rigorous mathematical derivation. It bears the following advantages: (1) providing an intuitive picture or illuminative insights; (2) helping grasp the key points from complicated details; (3) greatly simplifying many tedious, laborious, and error-prone calculations; and (4) able to double- Read More

In this communication we carry out an in-depth review of a very versatile QSPR-like method. The method name is MARCH-INSIDE (MARkov CHains Ivariants for Network Selection and DEsign) and is a simple but efficient computational approach to the study of QSPR-like problems in biomedical sciences. The method uses the theory of Markov Chains to generate parameters that numerically describe the structure of a system. Thi Read More