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Drug Target Screening and its Validation by Zebrafish as a Novel Tool

Omprakash G Bhusnure, Jyoti M Mane, Sachin B Gholve, Sanjay S Thonte, Padmaja S Giram and Jaiprakash N Sangshetti

Presently, the research using Zebrafish is expanding into areas such as pharmacology, clinical research as a disease model and interestingly in drug discovery. Mammalian models of absorption, distribution, metabolism and excretion (ADME)/pharmacokinetics and efficacy are expensive, laborious and consume large quantities of precious compounds. There is also increasing pressure to limit animal use to situations in which they are absolutely necessary, such as in preclinical toxicity and safety assessment. The use of Zebrafish in pharmaceutical research, drug discovery and development is mainly target screening, target identification, target validation and drug toxicity study. Zebrafish have recently entered the fray as a model animal for some human diseases. It has numerous attributes in toxicology studies and high throughput screening. The fish are more affordable, easier to keep, and faster to rise than mammals, giving a higher-throughput system. Perhaps surprisingly, genes that cause disease in zebrafish are similar to those in humans. Zebrafish being a non-mammalian, drugs can also be tested for toxicity and their potential therapeutic activity against the target more easily than in mammals. The Zebrafish embryo has become an important vertebrate model for assessing drug effects. It exhibits unique characteristics, including ease of maintenance and drug administration, short reproductive cycle and transparency that permits visual assessment of developing cells and organs. Using Zebrafish it is possible to obtain results quickly at lower costs. “Reducing failures early in development is far more important than filling a pipeline with poorly chosen late-stage products likely to fail, and fail expensively.”