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US 2004/0002119 A1Published application
Method of predicting cell-based assay results using binding profiles
OwnerMarie A. Iannone, Kenneth Hugh Pearce JR. +4inventors
InventorsMarie A. Iannone, Kenneth Hugh Pearce JR., Jean Shearin, Catherine Ann Simmons, Daniel Lee Svoboda, Dana Edward Vanderwall
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Abstract
A rapid method of characterizing interactions between compounds and biological molecules in vitro, in order to predict the in vivo characteristics of the compounds, is described. Preferably, the methods utilize labeled microspheres in multiplexed assays.
Claims16
A method of predicting the effect of a pharmaceutical compound in a cell-based assay that is responsive to modulation of a nuclear receptor, comprising:
- a) selecting a plurality of reference compounds whose effects in a cell-based assay are known, where said cell-based assay is responsive to modulation of a nuclear receptor;
- b) selecting a plurality of binding partners known to bind to said nuclear receptor;
- c) contacting said binding partners and said nuclear receptor in the presence of a reference compound, under conditions that allow binding, and detecting the extent of binding achieved, such that the compound's binding profile can be characterized by the relative differences between the binding results for that compound;
- d) repeating step (c) for each of said reference compounds;
- e) detecting, for at least one test compound whose effects in said cell-based assay are not known, the extent of binding of said nuclear receptor to each of said binding partners in the presence of said test compound, such that the test compound's binding profile can be characterized by the relative differences between the binding results for that compound;
- and
- f) comparing the binding profile of each reference compound to the binding profile of the test compound, to identify the reference compound having the binding profile that is most similar to the test compound binding profile;
- where identification of a reference compound binding profile that is similar to the test compound binding profile indicates that the test compound will achieve results in said cell-based assays that are similar to the results achieved by the reference compound.
5 more elements
A method of predicting the effect of a pharmaceutical compound in a cell-based assay that is responsive to modulation of a GPCR, comprising:
- a. selecting a plurality of reference compounds whose effects in a cell-based assay are known, said cell-based assay responsive to modulation of a G-protein coupled receptor (GPCR);
- b. selecting a plurality of binding partners known to bind to said GPCR;
- c. contacting said binding partners and said GPCR in the presence of a reference compound, under conditions that allow binding, and detecting the extent of binding achieved, such that the compound's binding profile can be characterized by the relative differences between the binding results for that compound;
- d. repeating step (c) for each of said reference compounds;
- e. detecting, for at least one test compound whose effects in said cell-based assay are not known, the extent of binding of said GPCR to each of said binding partners in the presence of said test compound, such that the test compound's binding profile can be characterized by the relative differences between the binding results for that compound;
- and
- f. comparing the binding profile of each reference compound to the binding profile of the test compound, to identify the reference compound having the binding profile that is most similar to the test compound binding profile;
- where identification of a reference compound binding profile that is similar to the test compound binding profile indicates that the test compound will achieve results in said cell-based assays that are similar to the results achieved by the reference compound.
5 more elements
A method of predicting the effect of a pharmaceutical compound in a cell-based assay that is responsive to modulation of a 7TM receptor, comprising:
- a. selecting a plurality of reference compounds whose effects in a cell-based assay are known, said cell-based assay responsive to modulation of a 7-transmembrane receptor (7TM receptor);
- b. selecting a plurality of binding partners known to bind to said 7TM receptor;
- c. contacting said binding partners and said 7TM in the presence of a reference compound, under conditions that allow binding, and detecting the extent of binding achieved, such that the compound's binding profile can be characterized by the relative differences between the binding results for that compound ;
- repeating step (c) for each of said reference compounds;
- d. for at least one test compound whose effects in said cell-based assay are not known, detecting the extent of binding of said 7TM receptor to each of said binding partners in the presence of said test compound, such that the test compound's binding profile can be characterized by the relative differences between the binding results for that compound;
- e. detecting, for at least one test compound whose effects in said cell-based assay are not known, the extent of binding of said 7TM to each of said binding partners in the presence of said test compound, such that the test compound's binding profile can be characterized by the relative differences between the binding results for that compound;
- and
- f. comparing the binding profile of each reference compound to the binding profile of the test compound, to identify the reference compound having the binding profile that is most similar to the test compound binding profile
- where identification of a reference compound binding profile that is similar to the test compound binding profile indicates that the test compound will achieve results in said cell-based assays that are similar to the results achieved by the reference compound.
6 more elements
A method of predicting the effect of a pharmaceutical compound in a cell-based assay that is responsive to modulation of an ion channel, comprising:
- a. selecting a plurality of reference compounds whose effects in a cell-based assay are known, said cell-based assay responsive to modulation of an ion channel;
- b. selecting a plurality of binding partners known to bind to said ion channel;
- c. contacting said binding partners and said ion channel in the presence of a reference compound, under conditions that allow binding, and detecting the extent of binding achieved, such that the compound's binding profile can be characterized by the relative differences between the binding results for that compound;
- repeating step (c) for each of said reference compounds;
- d. repeating step (c) for each of said reference compounds;
- e. detecting, for at least one test compound whose effects in said cell-based assay are not known, the extent of binding of said ion channel to each of said binding partners in the presence of said test compound, such that the test compound's binding profile can be characterized by the relative differences between the binding results for that compound;
- and
- f. comparing the binding profile of each reference compound to the binding profile of the test compound, to identify the reference compound having the binding profile that is most similar to the test compound binding profile;
- where identification of a reference compound binding profile that is similar to the test compound binding profile indicates that the test compound will achieve results in said cell-based assays that are similar to the results achieved by the reference compound.
6 more elements
Dependencies are inferred from the claim text.