Profiling library

Xie, P., Muresan, S., Li, J. CLASS - a high-throughput cheminformatic tool for chemical library profiling. Presented at ChemAxon s User Group Meeting 2005, Budapest Hungary, http //www. chemaxon.com/forum / downloads 82.ppt. 

I The use of computational methods such as reactant clustering and library profiling to maximize reactant diversity and optimize iarmacokinetic parameters has been described (132), with four-point pharmacophore... 

Major reasons for drug candidates to fail in early clinical phases are unpropitious pharmaco-kinetic properties (such as a lack of bioavailability) or toxicity. Therefore, estimation of these properties is an important part of a combinatorial library profile. An increasing number of publications [6, 42-45] demonstrate the importance of ADME parameters (ADME = absorption, distribution, metaboHsm, and ehmina-tion). Several commercial software packages are available. The ways in which ADME parameters are derived are similar in most available software products. In a first step, simple descriptors are calculated and in a second step, these descriptors are correlated with experimental data [46]. The parameters must describe properties that are important for pharmaco-kinetics (lipophilicity, size, and polarity of molecules, etc.). Standard correlation methods can be used, because the type of correlation has only secondary effects on the results. Generally, the predictivity of classification methods (the output from which can only be good or bad ) is slightly better compared to a quantitative correlation. 

AC Good, R Lewis. New methodology for profiling combinatorial libraries and screening sets Cleaning up the design process with HARPick. I Med Chem 40 3926-3936, 1997. 

Hazardous Substances Data Bank (HSDB) on compact disc from the Canadian Center for Occupational Health and Safety (can buy at CCOHS web site). "The HSDB(R) (Hazardous Substances Data Bank(R)) database contains data profiles on 4,500 potentially toxic chemical substances. It is created and updated by specialists at the U.S. National Library of Medicine. Compiled from an extensive range of authoritative sources, HSDB is widely recognized as a reliable and practical source of health and safety information. Much of the data is peer reviewed. 

Threading techniques try to match a target sequence on a library of known 3D structures by threading the target sequence over the known coordinates. In this manner, threading tries to predict the 3D structure starting from a given protein sequence. It is sometimes successful when comparisons based on sequences or sequence profiles alone fail due to a too low sequence similarity. 

Leach AR, Bradshaw J, Green DVS, Hann MM, Delany JJ III. Implementation of a system for reagent selection and library enumeration, profiling and design. / Chem Inf Comput Sci 1999 39 1161-72. 

Root DE, Flaherty SP, Kelley BP, Stockwell BR. Biological mechanism profiling using an annotated compound library. Chem Biol 2003 10 881-92. 

Cases M, Garcia-Serna R, Hettne K, Weeber M, van der Lei J, Boyer S, Mestres J. Chemical and biological profiling of an annotated compound library directed to the nuclear receptor family. Curr Top Med Chem 2005 5 763-72. 

The safety professional s online library, covering topics related to safety, safety management, ergonomics, fleet and environment. The Safety Library contains over 40 environmental databases and over 70 databases of chemical profiles. Subscription is required. 

Monge, A., Arrault, A., Marot, C., Morin-AUory, L. Managing, profiling and analyzing a library of 2.5 million compounds gathered from 32 chemical providers. Mol. Diversity 2006, 10, 389-403. 

Obviously, use of such databases often fails in case of interaction between additives. As an example we mention additive/antistat interaction in PP, as observed by Dieckmann et al. [166], In this case analysis and performance data demonstrate chemical interaction between glycerol esters and acid neutralisers. This phenomenon is pronounced when the additive is a strong base, like synthetic hydrotalcite, or a metal carboxylate. Similar problems may arise after ageing of a polymer. A common request in a technical support analytical laboratory is to analyse the additives in a sample that has prematurely failed in an exposure test, when at best an unexposed control sample is available. Under some circumstances, heat or light exposure may have transformed the additive into other products. Reaction product identification then usually requires a general library of their spectroscopic or mass spectrometric profiles. For example, Bell et al. [167] have focused attention on the degradation of light stabilisers and antioxidants... 

Table 5.9 summarises the main features of FTIR spectroscopy as applied to extracts (separated or not). Since many additives have quite different absorbance profiles FTIR is an excellent tool for recognition. Qualitative identification is relatively straightforward for the different classes of additives. Library searching entails a sequential, point-by-point, statistical correlation analysis of the unknown spectrum with each of the spectra in the library. Fully automated analysis of... 

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