Download PDF by Darrell R. Boverhof, B. Bhaskar Gollapudi: Applications of Toxicogenomics in Safety Evaluation and Risk

By Darrell R. Boverhof, B. Bhaskar Gollapudi

ISBN-10: 0470449829

ISBN-13: 9780470449820

This ebook presents a well timed evaluate of toxicogenomics, with detailed emphasis at the functional functions of this know-how to the chance evaluate approach. Introductory sections are via a chain of chapters highlighting sensible and systematic purposes of toxicogenomics in informing the chance overview procedure – together with the parts of mutagenicity, carcinogenicity, endocrine toxicity, organ-specific toxicity, inhabitants tracking, and ecotoxicology. The publication concludes with methods for the combination of this know-how in defense review stories, and an outlook on how toxicogenomics and complementary applied sciences can reframe the present danger evaluate paradigm.

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2) and the widely used generic dilthiazem (see Fig. 3). The two main advantages of the process, which was developed by DSM, are operational simplification (much smaller plant, ten times higher throughput) and cost savings on raw materials, mainly 2-aminothiophenol, which is used in a later stage in the process. The resulting cost reduction of the API is 40%. Further examples of blockbuster drugs for which enzymes are used in the synthesis, are Pfizer’s Lipitor (atorvastatin), for which the pivotal intermediate (R)-3-hydroxy-4-cyanobutyrate is now made with a nitrilase, and Merck’s Zocor (simvastatin) and Singulair (montelukast), for which the reduction of a ketone to an S alcohol, which required stoichiometric amounts of expensive and moisturesensitive ‘‘(–)-DIP chloride’’ has now been replaced by a ketoreductase enzyme catalyst step.

Enzymes are differentiated from chemical catalysts particularly with regard to stereoselectivity, regioselectivity, and chemoselectivity. Whereas they were traditionally associated with the metabolic pathway of natural substances, they can also be tailored for use in chemical synthesis. Biocatalysts are applied like chemical catalysts, either in solution or on solid supports. Immobilized enzymes can be recovered by filtration after completion of the reaction. Conventional plant equipment can be used with minor adaptations.

A starting material is converted by the biocatalyst to the desired product. Enzymes are differentiated from chemical catalysts particularly with regard to stereoselectivity, regioselectivity, and chemoselectivity. Whereas they were traditionally associated with the metabolic pathway of natural substances, they can also be tailored for use in chemical synthesis. Biocatalysts are applied like chemical catalysts, either in solution or on solid supports. Immobilized enzymes can be recovered by filtration after completion of the reaction.

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Applications of Toxicogenomics in Safety Evaluation and Risk Assessment by Darrell R. Boverhof, B. Bhaskar Gollapudi


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