Pharmacological profiling of drugs with cell-based assays

A method for establishing safety profiles for chemical compounds, said method comprising (A) testing the effects of said chemical compounds on the amount and/or post-translational modifications of two or more macromolecules in intact cells;

• (B) constructing a pharmacological profile based on the results of said tests;
• and (C) comparing said profile to the profile(s) of drugs with established safety characteristics.

A method for establishing toxicity profiles for chemical compounds, said method comprising (A) testing the effects of said chemical compounds on the amount and/or post-translational modifications of two or more macromolecules in intact cells;

• (B) constructing a pharmacological profile based on the results of said tests;
• (C) comparing said profile to the profile(s) of drugs with known adverse or toxic characteristics.

A method for identifying the cellular pathways underlying drug toxicity, said method comprising (A) testing the effects of toxic compounds on the amount and/or the post-translational modifications of two or more macromolecules in intact cells;

• and (B) using the results of said tests to identify patterns of modifications associated with toxicity.

A method for performing pharmacological profiling of a chemical compound, said method comprising (a) constructing a panel of cell-based assays, wherein said assays comprise the amount and/or post-translational modifications of two or more macromolecules;

• (b) contacting said cells with said chemical compound;
• (c) measuring the amount and/or the subcellular location of the signals in said cells with said cell-based assays;
• (d) using the result of (c) to construct a pharmacological profile for said compound.

A method for performing pharmacological profiling of a chemical compound, said method comprising (a) constructing a panel of immunofluorescence assays in intact cells;

• (b) contacting said cells with said chemical compound;
• (c) quantifying the fluorescence signals in the members of said panel;
• (d) using the result of (c) to construct a pharmacological profile for said compound.

An assay panel, said panel comprising immunofluorescence assays for the amount and/or post-translational modifications of two or more macromolecules, wherein said assays are performed by automated microscopy or automated image analysis.

A composition comprising an assay panel, said panel comprising high-content assays for the amount and/or post-translational modifications of two or more proteins.

A composition comprising an assay panel, said panel comprising at least one high-content assay for the amount and/or post-translational modification of a protein and at least one high-content assay for the amount and/or subcellular location of a protein-protein interaction.

A composition comprising an assay panel, said panel comprising at least one assay that is an immunofluorescence assay and at least one assay that is a non-immunofluorescence assay.

A panel of high-content cell-based assays, said panel comprising two or more antibodies, wherein at least one antibody is selected from the list shown in Table 1.