SBIR-STTR Award

Cytochrome P450 (CYP) enzymes catalyze the majority of known drug metabolism and the bulk of these reactions occur in the liver. As a consequence, many clinically relevant drug-drug interactions are associated with inhibition and/or induction of a specific CYP enzyme. Modifications of CYP activities can have profound effects on therapeutic efficacy and can lead to life-threatening toxicity. In order to provide an early warning system for potential serious side effects, detection of specific CYPs responsible for drug metabolism and drug-drug interactions is a goal of all pre-clinical studies. An ideal CYP assay should be rapid, robust, reliable, reproducible, and amenable to automation in multiwell plate formats. This research will develop a microplate format high throughput whole zebrafish CYP functional assay for assessing drug metabolism and drug safety. Based on genetic and physiological similarity to humans, zebrafish show promise as an efficient, predictive animal model for assessing drug metabolism and drug safety. The zebrafish assay will facilitate detection of specific cytochromes responsible for drug metabolism and drug-drug interactions, and provide an early warning system for potential serious side effects,

Thesaurus Terms:
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Cytochrome P450 (CYP) enzymes catalyze the majority of known drug metabolism and the bulk of these reactions occur in the liver. As a consequence, many clinically relevant drug-drug interactions are associated with inhibition and/or induction of a specific CYP enzyme. Modifications of CYP activities can have profound effects on therapeutic efficacy and can lead to life-threatening toxicity. In order to provide an early warning system for potential serious side effects, detection of specific CYPs responsible for drug metabolism and drug-drug interactions is a goal of all pre-clinical studies. An ideal CYP assay should be rapid, robust, reliable, reproducible, and amenable to automation in multiwell plate formats. This research will develop a microplate format high throughput whole zebrafish CYP functional assay for assessing drug metabolism and drug safety. Based on genetic and physiological similarity to humans, zebrafish show promise as an efficient, predictive animal model for assessing drug metabolism and drug safety.

Public Health Relevance:
Project Narrative The zebrafish assay will facilitate detection of specific cytochromes responsible for drug metabolism and drug-drug interactions, and provide an early warning system for potential serious side effects,

Public Health Relevance Statement:
Project Narrative The zebrafish assay will facilitate detection of specific cytochromes responsible for drug metabolism and drug-drug interactions, and provide an early warning system for potential serious side effects,

Project Terms:
Adverse effects; Affect; Animal Model; Animal Models and Related Studies; Animals; Assay; Automation; Bioassay; Bioavailability; Biologic Assays; Biologic Availability; Biological Assay; Biological Availability; Brachydanio rerio; Buckminsterfullerenes; Buckyballs; CP33; CP34; CPC9; CPD6; CYP; CYP2C10; CYP2C9; CYP2C9 gene; CYP2D; CYP2D6; CYP2D6 gene; CYP2DL1; CYP3; CYP3A; CYP3A13; CYP3A3; CYP3A4; CYP3A4 gene; CYPIIIA4; Collection; Common Rat Strains; Complex; Cytochrome P-450; Cytochrome P-450 Enzyme System; Cytochrome P450; Cytochromes; Danio rerio; Detection; Drug Evaluation, Preclinical; Drug Interactions; Drug Screening; Drugs; Enzymes; Evaluation; Evaluation Studies, Drug, Pre-Clinical; Evaluation Studies, Drug, Preclinical; Exhibits; FDA approved; Family; Family member; Fullerenes; Genetic; Goals; Government; HLP; Hepatic; Hepatic Cells; Hepatic Parenchymal Cell; Hepatocyte; Human; Human, General; In Vitro; Intermediary Metabolism; Lead; Libraries; Life; Liquid substance; Liver; Liver Cells; METBL; Mammalia; Mammals; Mammals, General; Mammals, Mice; Mammals, Rats; Man (Taxonomy); Man, Modern; Medication; Metabolic Clearance Rate; Metabolic Processes; Metabolism; Mice; Modeling; Modification; Murine; Mus; NF-25; P450; P450 MP-4; P450 PB-1; P450-DB1; P450-PCN1; P450C2D; P450C3; P450IIC9; P450PCN1; Pb element; Persons; Pharmaceutic Preparations; Pharmaceutical Agent; Pharmaceutical Preparations; Pharmaceuticals; Pharmacologic Substance; Pharmacological Substance; Phase; Physiologic; Physiologic Availability; Physiological; Preclinical Drug Evaluation; Preclinical Testing; Process; Rat; Rattus; Reaction; Reliance; Research; SBIR; SBIRS (R43/44); Safety; Screening procedure; Small Business Innovation Research; Small Business Innovation Research Grant; System; System, LOINC Axis 4; Technology; Testing; Therapeutic Agents; Toxic effect; Toxicities; Transgenic Mice; Transgenic Organisms; Treatment Efficacy; Treatment Side Effects; Zebra Danio; Zebra Fish; Zebrafish; base; bioavailability of drug; body system, hepatic; clearance rate; clinical relevance; clinically relevant; cost; drug candidate; drug discovery; drug metabolism; drug use screening; drug/agent; fluid; heavy metal Pb; heavy metal lead; in vivo; inhibitor; inhibitor/antagonist; liquid; model organism; mouse model; organ system, hepatic; preclinical study; public health relevance; screening; screenings; side effect; success; therapeutic efficacy; therapeutically effective; therapy adverse effect; transgenic; treatment adverse effect