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SIGMA Introduces World's First Suite of Knockout Rats for ADME/Tox Applications

Merck
9 Mar 2010
Sarah Sarah
Marketing / Sales

Product news

Sigma® Life Science today extended its portfolio of knockout rat models with the announcement of a new suite of models designed to facilitate more predictive absorption, distribution, metabolism, excretion and toxicity (ADME/Tox) studies. This enlargement of our product offerings, the first ever models created especially for ADME/Tox applications, is expected to help researchers establish the efficacy of drugs more rapidly and with greater accuracy due to the rat’s ability to better model human physiology when compared to mouse models currently used.

The four new models were developed by Sigma Advanced Genetic Engineering (SAGE™) Labs, a Sigma Life Science initiative, and have single gene deletions to well-established drug transporters: Mdr1a (P-glycoprotein), Mrp1 (Multiple drug resistance-associated protein 1), Mrp2 (Multiple drug resistance-associated protein 2), Pxr (Pregnane X receptor), and Bcrp (Breast cancer resistance protein). The validated Mdr1a knockout model is currently available for purchase, while the other models are expected to be available for purchase later this year.

“Until now, the availability of relevant, genetically modified rats was limited. Knockout mice are readily available, but very challenging to use in ADME/tox applications due to their size and physiology. We’ve changed that,” commented Dr. Edward Weinstein, director of SAGE Labs. “Our knockout rat models offer a platform that can potentially save millions of dollars in development costs for potential drug candidates, by providing a more human-like model, and at the same time significantly decrease time to market for these therapeutics. A rat that is deficient in P-glycopotein (PGP) expression, for example, serves as an improved model over the existing mouse model due to its metabolism and physiology, making it more predictive of how a drug will behave in humans. This is of huge benefit to drug discovery, enabling researchers to go back and address issues much sooner than they can today.”

The latest knockout rat models were developed using Sigma-Aldrich’s proprietary CompoZr™ Zinc Finger Nuclease (ZFN) gene editing technology, which enables scientists to deactivate or ‘knockout’ specific genes that are associated with human disease.

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ProteomicsProteomics is the systemic bioinformatics study of proteins and amino acids, including their structure, size, function and identification. Tools used in proteomics include chromatography, blotting and gels, protein arrays, mass spectrometry and ELISA and associated analysis software. Analyzers and proteomic systems should be sensitive, high resolution, fast and may be automated for high-throughput.ADME-ToxicologyADME-toxicology (ADME-Tox) studies are used in pharmacology and pharmacokinetics to assess the activity/toxicity of drugs <i>in vivo</i> or <i>in vitro</i>. Find bioassays for absorption, distribution, metabolism, and excretion of drug molecules including cytotoxicity, transporter/permeability, metabolism and activity assays as well as hepatocytes and cell lines for ADME. Find the best ADME-toxicology products in our peer-reviewed product directory: compare products, check customer reviews and receive pricing direct from manufacturers.Medicinal ChemistryMedicinal chemistry is a broad discipline encompassing the design, identification, synthesis and development of chemicals in drug discovery. It includes a number of techniques covering structural biology, synthetic chemistry and molecular biology. Technologies used in medicinal chemistry include ADME, lab-on-a-chip, high content screening and assay assembly.Process ChemistryProcess chemistry is an important stage of drug development for scaling-up drug production or chemical synthesis reactions. It is useful for optimizing economical and efficient drug production. Process chemistry uses reactors and pump systems as well as reagents, standards and buffers.Protein PurificationProtein purification is a vital step in drug discovery, therapeutics, biotech and life science research. The purification process typically involves subcellular or membrane protein extraction with cell lysis kits, separation of proteins from cell debris by filtration or spin columns, and the isolation of proteins of interest from other proteins and impurities with affinity purification (including fusion protein tags and antibody binding proteins A, G and L), immunoprecipitation or chromatographic methods, such as ion exchange, size exclusion and immobilized metal affinity chromatography. All purification methods come in multiple formats for your laboratory needs, including agarose or magnetic beads, resins, columns and filter plates. Find the best protein purification equipment in our peer-reviewed product directory: compare products, check customer reviews and receive pricing direct from manufacturers.Clinical TrialsClinical Trials, an essential part of drug discovery process, assess the safety and effectiveness of a new medication or device in the pharmaceutical industry. Clinical Trials are a phased process (Phase 0, Phase I, Phase II, Phase III and Phase IV) which begins after initial preclinical testing.

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