Drug discovery & developmentWorkdom2020-08-24T10:09:19+00:00
The pre-clinical drug discovery and development process encompasses the early phases of research designed to understand the mechanisms of the disease through preclinical in vitro and in vivo safety assessment to determine if a drug is ready for clinical trials. Target identification and validation often involves high throughput screening as well as high content screening to determine if a target can be manipulated by the drug. Following lead optimization drug candidates are screened for efficacy as well as adsorption, distribution, metabolism, excretion and toxicity (ADME/Tox). In vitro high throughout drug discovery is becoming more popular due its cost effectiveness and ever appreciating relevance. On the forefront of this movement is in vitro toxicity screening for the pharmaceutical and chemical industry. New high throughout assays and cell lines are being developed to address toxicity problems. Once a xenobiotic is identified as positive for a toxicity readout it ican be further investigated via in vivo animal models.
Genetically engineered immunodeficient rat models to create ‘humanized’ liver rat models. These humanized models are capable of predicting human specific hepatotoxicity which plays a significant role in drug failure rates. Immunodeficient rats are also designed to accept human cancer xenografts for oncology drug efficacy testing provide several unique advantages over mouse models. First, the larger size of the animals allows for easier handling and surgical manipulations especially for intracranial xenografts and other tissue specific tumor injections. Secondly, xenograft tumors can grow larger in rats providing a larger amount of tissue/material to work with and these can be more easily studied with non-invasive imaging to track in-vivo tumor growth and metastasis, which is often more representative of the human cancer progression compared to mouse PDXs. Additionally, since rats are the ideal model for toxicology, both efficacy and toxicity can be studied in the same species.
Clinically relevant pre-clinical in vitro and in vivo assays and that apply to both discovery efficacy testing and toxicity/safety assessment are required for successful drug development.