Methods of identifying non-specific inhibitors of biomolecules

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or...

Reexamination Certificate

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Reexamination Certificate

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06887658

ABSTRACT:
The present invention provides methods of identifying compounds that non-specifically inhibit biological reactions. The present invention further includes kits that facilitate this identification. In addition, complications of compounds for use in high throughput drug screening that have been evaluated by the disclosed methodology are also part of the present invention. Further, the invention provides methods for identifying a false positive compound previously identified as positive in a screening assay by measuring the activity of at least one biological activity in the presence and absence of a small molecule compound capable of inhibiting aggregate formation, e.g., digitonin.

REFERENCES:
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Patera, et al., Crystal Structures of Substrate and Inhibitor Complexes with AmpC β-Lactamase: Possible Implications for Substrate-Assisted Catalysis, J. Am. Chem. Soc. 122: 10504-10512 (2000).
Rishton, G.M., Reactive Compounds and in vitro False Positives in HTS, Drug Discovery Today, 2: 382-384 (1997).
Roche, et al., Development of a Virtual Screening Method for Identification of “Frequent Hitters” in Compound Libraries, J. Med. Chem. 45: 137-142 (2002).
Stopa, et al., Supramolecular Ligands: Monomer Structure and Protein Ligation Capability, Biochimie, 80:963-968 (1998).
Luo et al., Molecular and Cellular Biology, 21:5678-5687 (2001).
Miller et al., Protein Sci., 6:2166-2179 (1997).
Patera et al., 122:10504-10512 (2000).
Rishton, Drug Discovery Today, 2:382-384 (1997).
Roche et al., J. Med. Chem., 45:137-142 (2002).
Stopa et al., Biochimie, 80:963-968 (1998).

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