Abstract: The present invention provides high throughput screening systems for identifying compounds that modulate the biological activity of a biochemically functional sarcomere. The method can be performed in plurality simultaneously with fluorescence or absorbance readouts.

Abstract: Described herein are methods which identify candidate agents as binding to a protein or as a modulator of the binding characteristics or biological activity of a protein. Generally, the methods involve the use of ADP or phosphate. The assays can be used in a high throughput system to obviate the cumbersome steps of using gels or radioactive materials.

Abstract: 1,2,4-Triazin-5-ones useful for treating cellular proliferative diseases and disorders by modulating the activity of KSP are disclosed.

Abstract: Methods and apparatus are provided for the analysis of images of cells and extraction biologically-significant shape-related features from the cell images. The extracted features may be correlated with particular conditions induced by biologically-active agents with which cells have been treated, thereby enabling the automated analysis of cells based on cell shape parameters. In particular, the invention provides methods for segmentation of cells in an image using a combination of a reference component image data and cell shape-indicative marker image data in a watershed technique. Further, the invention provides a skeletonization and skeleton analysis technique for extracting biologically-relevant features from cell shapes.

Abstract: The invention provides isolated nucleic acid and amino acid sequences of HsKip3, antibodies to HsKip3, methods of screening for HsKip3a modulators using biologically active HsKip3, and kits for screening for HsKip3a modulators.

Abstract: A method for calculating distances between stimulus response curves (e.g., dose response curves) allows classification of stimuli. The response curves show how the phenotype of one or more cells changes in response to varying levels of the stimulus. Each “point” on the curve represents quantitative phenotype or signature for cell(s) at a particular level of stimulus (e.g., dose of a therapeutic). The signatures are multivariate phenotypic representations of the cell(s). They include various features of the cell(s) obtained by image analysis. To facilitate the comparison of stimuli, distances between points on the response curves are calculated. First, the response curves may be aligned on a coordinate representing a separate distance, r, from a common point of negative control (e.g., the point where no stimulus is applied). Integration on r may be used to compute the distance between two response curves. The distance between response curves is used to classify stimuli.

Abstract: Cell based assays are used to assess the hepatotoxicity of a stimulus. Imaging technologies are used to analyze the effects of a stimulus on hepatocytes. Image analysis may characterize the stimulus on the basis of whether it is hepatotoxic, and if so what type of pathology is exhibited; e.g., apoptosis, necrosis, cholestasis, and/or steatosis.

Abstract: Image analysis methods and apparatus are used for determination of the ploidy of cells. The methods may involve segmenting an image to identify one or more discrete regions occupied by cells or nuclei, determining the presence of a particular ploidy indicator feature within the region(s), and providing a value of the indicator feature to a model that classifies cells' ploidy on the basis of the indicator feature. In some embodiments, the indicator feature is a level of DNA in a cell. In certain embodiments, the method further comprises treating one or more cells with a marker that highlights the ploidy indicator feature. In certain embodiments, the cells are treated prior to producing one or more images of the one or more cells. In certain embodiments, the ploidy indicator feature comprises DNA and the marker co-locates with DNA and provides a signal that is captured in the image. In certain embodiments, the signal comprises a fluorescent emission.

Abstract: The present invention provides high throughput screening methods for characterizing compounds that modulate the biological activity of a biochemically functional sarcomere. Compounds characterized by such methods are useful for treating congestive heart failure.

Abstract: Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of KSP are disclosed.

Abstract: Described herein are methods which identify candidate agents as binding to a protein or as a modulator of the binding characteristics or biological activity of a protein. Generally, the methods involve the use of ADP or phosphate. The assays can be used in a high throughput system to obviate the cumbersome steps of using gels or radioactive materials.

Abstract: The present invention provides intermediates, synthetic methods and novel urea compositions of matter.

Abstract: Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of KSP are disclosed.

Abstract: The present invention provides novel quinazolinone compositions of matter comprising enantiomerically pure compound represented by Formula I: or a pharmaceutically acceptable salt thereof, having a detectable amount of one or more starting material and/or reagent used in the synthesis thereof.

Abstract: According to the present invention, computer based techniques for using information technology in therapeutics or drug discovery. In an exemplary embodiment, computer based techniques for determining information about the properties of substances based upon information about structure of living or non-living cells exposed to substances are provided. Computer software according to the present invention enables researchers and/or scientists to identify promising candidates in the search for new and better medicines or treatments using, for example, a cellular informatics database.

Abstract: Methods, code and apparatus analyze cell images to automatically identify and characterize the Golgi complex in individual cells. This is accomplished by first locating the cells in the image and defining boundaries of those cells that subsume some or all of the Golgi complex of those cells. The Golgi complex in the images typically have intensity values corresponding to the concentration of a Golgi component in the cell (e.g. a polysaccharide associated with the Golgi complex). The method/system then analyzes the Golgi components of the image (typically on a pixel-by-pixel basis) to mathematically characterize the Golgi complex of individual cells. This mathematical characterization represents phenotypic information about the cells' Golgi complex and can be used to classify cells. From this information, mechanism of action and other important biological information can be deduced.

Abstract: Compounds, compositions and methods useful for treating cellular proliferative diseases and disorders, for example, by modulating the activity of KSP, are disclosed.

Abstract: The present invention provides assays for detecting ADP, GDP and inorganic phosphate. These assays can be used directly to detect the presence of ADP, GDP and inorganic phosphate or can be used as part of a number of methods for identifying candidate agents that bind to a target protein or serve as modulators of the biological activity of a target protein.

Abstract: According to the present invention, computer based techniques for using information technology in therapeutics or drug discovery. In an exemplary embodiment, computer based techniques for determining information about the properties of substances based upon information about structure of living or non-living cells exposed to substances are provided. Computer software according to the present invention enables researchers and/or scientists to identify promising candidates in the search for new and better medicines or treatments using, for example, a cellular informatics database.

Abstract: Phenothiazine derivatives of formula (I) are disclosed. The compounds are inhibitors of the mitotic kinesin KSP and are useful in the treatment of cellular proliferative diseases, such as cancer, hyperplasias, restenosis, cardiac hypertrophy, immune disorders and inflammation.