Drug metabolism problems such as production of toxic metabolites and unfavorable pharmacokinetics cause almost half of all drug candidate failures during clinical trials. Although glucuronidation is one of the most important routes of drug metabolism, the broad and overlapping substrate specificity… More

Drug metabolism problems such as production of toxic metabolites and unfavorable pharmacokinetics cause almost half of all drug candidate failures during clinical trials. Although glucuronidation is one of the most important routes of drug metabolism, the broad and overlapping substrate specificity… More

DESCRIPTION (provided by applicant): Drug metabolism problems such as drug-drug interactions and production of toxic metabolites cause almost half of all drug candidate failures during clinical trials. Sulfation is an important type of conjugative drug metabolism that is also used to regulate the… More

DESCRIPTION (provided by applicant): This Phase II proposal is for a collaborative effort between Dr. Richard Weinshilboum of the Mayo Institute and BellBrook Labs, LLC to translate basic pharmacogenetics research on conjugative drug metabolizing enzymes into molecular screening assays that can be… More

DESCRIPTION (provided by applicant): There are more than 400 distinct protein kinases encoded in the human genome; elucidating their role in disease and identifying selective inhibitors is a major pharma initiative. Kinase malfunction has been linked to all of the most important therapeutic areas,… More

DESCRIPTION (provided by applicant): Discovery of improved therapies for breast cancer will require assay systems that accurately recapitulate the cellular signaling of intact mammary tissue. To reconstitute mammary tissue structure and function faithfully in vitro, we will develop a microfluidic… More

DESCRIPTION (provided by applicant): There are over 500 protein kinases in the human genome and several hundred other enzymes that utilize ATP as a phosphate donor or energy source. Protein kinases are the second most intensively screened target class, with links to all of the major therapeutic… More

DESCRIPTION (provided by applicant): Methylation is a ubiquitous covalent modification used to control the function of diverse biomolecules including hormones, neurotransmitters, xenobiotics, proteins, nucleic acids and lipids. More than 50 distinct methyltransferase (MTs) enzymes are present in… More

DESCRIPTION (provided by applicant): More than 50% of drugs on the market target G protein-coupled receptors (GPCRs). Among the most important of these are drugs used to treat neurological disorders, such as pain relievers, antidepressants and anti-psychot ics, as well drugs used for… More

DESCRIPTION (provided by applicant): Neutrophil recruitment is a central component of inflammation, and there is intense focus on inhibiting the process both for chronic inflammatory disorders and for conditions where inflammation plays a contributory role , such as atherosclerosis. Chemotaxis - the… More

DESCRIPTION (provided by applicant): There is a strong need in drug discovery for cellular assays that better predict human responses to drugs. A key technical hurdle has been the difficulty of incorporating complex tissue architecture and cellular microen vironments into an assay format that is… More

DESCRIPTION (provided by applicant): Methylation is a ubiquitous and reversible covalent modification used to control the function of diverse biomolecules including their activity, stability and localization. Like phosphorylation, methylation is used to mo dulate protein function, but in addition… More

DESCRIPTION (provided by applicant): There is a high level of pharmaceutical interest in targeting enzymes that catalyze oxidation and reduction reactions for therapeutic intervention. Validated redox enzyme targets include HMG-CoA reductase, the target of statin drugs like Lipitor that are used to… More

DESCRIPTION (provided by applicant): In less than one year the 1918 Spanish flu pandemic claimed over 20 million lives worldwide, killing 675,000 Americans, more than 10 times the number of deaths to US servicemen in World War I. A similar strain of the vi rus that caused the 1918 pandemic could… More

DESCRIPTION (provided by applicant): There is a strong need in drug discovery for cellular assays that better predict human responses to drugs. A key technical hurdle has been the difficulty of incorporating 3-dimensional extracellular matrix into a powerf ul assay format that is compatible with the… More

DESCRIPTION (provided by applicant): Kinases are the most intensively screened class of enzymes being targeted for therapeutic intervention because of their central role in regulating the function of other biomolecules. Strategies for developing selective kinase inhibitors are evolving rapidly,… More

DESCRIPTION (provided by applicant): More than 50% of drugs on the market target G protein-coupled receptors (GPCRs). Among the most important of these are drugs used to treat neurological disorders, such as pain relievers, antidepressants and anti-psychot ics, as well drugs used for… More

DESCRIPTION (provided by applicant): Leukocyte recruitment is central to inflammation, and there is intense focus on inhibiting the process both for chronic inflammatory disorders and for conditions where inflammation plays a contributory role, such as ath erosclerosis. Whereas current… More

Current research tools to understand tumor cell migration and metastases are limited to linear gradients or constant flow across cells skewing results. Researchers at the National Institute of Standards and Technology developed a tool called the microfluidic palette which exposes cells to chemical… More

DESCRIPTION (provided by applicant): Key elements of tumorigenesis are driven by paracrine signaling between stromal and epithelial cells within the context of the extracellular matrix. Unfortunately, the cellular assays used for drug discovery typically r ely on a single cell type grown as a… More

DESCRIPTION (provided by applicant): There is a strong need for more predictive cellular assays that better represent the tissue that is under investigation. For airway epithelia such a model exists, and uses primary cells grown at an air liquid interface (ALI). A key technical hurdle has been the… More

DESCRIPTION (provided by applicant): Post translational modifications (PTMs) such as phosphorylation, glycosylation and methylation play a central and ubiquitous role in cellular signal transduction, and the enzymes that catalyze these reactions such as kinases and methyltransferases are the targets… More

DESCRIPTION (provided by applicant): Approaches to drug screening typically involve dramatic compromises in order to achieve high throughput and hold down costs. Examples include the use of immortalized, heterologous cell lines, and genetic engineering toover-express the target protein and/or… More