SBIR-STTR Award

The assessment of the toxicity of chemical compounds is an often critical and rate limiting component in their commercial development. The currently established regulatory environment demands that most if not all toxicity testing needed to provide required margins of safety be completed in animal models and, in the case of pharmaceuticals, in human clinical trials. There is currently a need to develop and validate credible in vitro toxicity endpoints that parallel the known effects of compounds in humans. The goal of this NIH SBIR Phase I Grant Application is to provide an initial framework for a validated in vitro toxicity database that can be utilized by the pharmaceutical, chemical, agricultural and biotechnology industries. Once complete, this database will be employed to aid in evaluating the safety characteristics of new chemical agents that may be administered to humans or animals as therapeutics or that pose significant exposure potential to human populations through their use. Specifically, we will : i) define and validate the use of immortalized cell lines to detect and parallel in vivo toxicity patterns, ii) evaluate several in vitro endpoints of neuronal toxicity in predicting in vitro neurotoxicity, iii) establish an initial data- base of in vitro toxicity of drugs and chemical compounds, and iv) initiate development of analytical tools to mine the in vitro database to provide predictive toxicity information about new chemical entities prior to in vivo testing. PROPOSED COMMERCIAL APPLICATIONS: This research will provide an initial dataset and validation of in vitro toxicology endpoints that can be employed by the pharmaceutical, chemical and agricultural industries in the development of commercial compounds. It will speed the development of new active agents and will in part remove the expensive and problematic issues of in vivo toxicology at an early stage in compound development. This dataset will be merged into a larger content database currently being constructed by NovaScreen that includes comprehensive receptor and enzyme data as well as extensive chemical and pharmacological information.

Thesaurus Terms:
chemical information system, computer system design /evaluation, data management, neurotoxicology, neurotoxin chemical structure /function, cytotoxicity, drug screening /evaluation, informatics cell line, tissue /cell culture

The goal of this NIH SBIR Phase II Grant Application is to expand and validate the pilot in vitro neurotoxicity database that was constructed during a Phase I SBIR Grant. The toxicity database will be used to aid in evaluating the safety characteristics of new chemical compounds that may be therapeutically administered to humans or that pose significant exposure potential to human populations through their use. Commercially, this database will be offered by NOVASCREEN Biosciences Corp. to the pharmaceutical, chemical, agricultural and biotech industries to reduce costs and streamline their toxicity testing requirements. The scope of this Phase II will be further in vitro toxicity testing of a select group of compounds used in Phase I and the screening of an additional 800 new compounds in two cell lines that are of neural origins. This testing will include assays that measure cellular growth, metabolism, respiration, viability and apoptosis. Annotations derived from the literature on animal and human in vivo toxicity testing standard compounds as well as assay data from NOVASCREEN's own proprietary receptor screening database (RSM) will be incorporated into this toxicity database.

Thesaurus Terms:
computer system design /evaluation, data management, neurotoxicology, neurotoxin, toxicology information system chemical information system, chemical structure function, cytotoxicity, drug screening /evaluation, informatics cell line, human subject, tissue /cell culture