Activity-based Proteomics for Toxicological Analysis

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 2R44CA097462-02
Agency Tracking Number: CA097462
Amount: $1,062,700.00
Phase: Phase II
Program: SBIR
Awards Year: 2003
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (858) 526-2511
Business Contact
Phone: (858) 526-2502
Research Institution
DESCRIPTION (provided by applicant): ActivX Biosciences (ActivX) will develop and validate a novel toxicoproteomics platform to correlate changes in protein activity with compound toxicology. This platform uses fluorescent chemical probes to interrogate catalytically active proteins related by super-family derived from any biological sample. Alterations in protein activity are expected to be more interpretable and relevant to toxicant molecular mechanism than the more commonly used transcript-profiling approaches. This Phase II study will demonstrate the utility of this protein activity platform. This study has several stages. 1) The platform will be established as a predictive platform for compound toxicity by investigating protein activities of a) cell lines and b) tissues from animals exposed to compounds that have been well-studied using pharmacology, genomics, and other techniques. 2) The resulting protein activity profiles will be integrated into a database that also includes publicly available transcription data, and will allow for seamless correlation of treatments with changes in protein activity levels of the serine hydrolase, cysteine protease, kinase, epoxide hydrolase, and glutathione-S-transferase families. The activity-based probes (ABPs) for some of these enzyme families are cell-permeable, which is a useful feature that allows for in vivo, rather than in vitro measurements of protein activity in cell lines. 3) Cell-permeable derivatives of ABPs that are currently not cell permeable will be synthesized. 4) To expand the breadth of our profiling abilities, ActivX will also design, synthesize and validate ABPs for the phosphatase and cytochrome P450 families. This platform will be useful for detecting toxicity of chemicals, including therapeutics, and will be important for classifying and exploring the molecular basis of toxicities. Therefore, this technology has a great potential for reducing the time and cost in early compound development, and for revealing underlying toxicity mechanisms of different compounds. ActivX plans to commercialize its technology by establishing a toxicoproteomic database, and by providing a service to the pharmaceutical industry that will detect toxicities of compounds early in the drug screening process.

* Information listed above is at the time of submission. *

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