Abstract
Despite many advances made in disease mechanisms knowledge and drug discovery and development processes, the election of promising lead compounds continues to be a challenge. Efficient techniques are required for lead selection of hit compounds selected through in vitro pharmacological studies, in order to generate precise low cost throughput data with minimal amount of compound to support the right decision making. In this context, the selection of lead compounds with physicochemical parameters that will benefit orally bioavailable drugs are crucial for patients compliance and cost effectiveness, as well as for successful pharmacology. A concept based in Lipinskis rules point out the importance of analyzing these informations in early stages. A hepatocyte screening system may provide data on many processes such as drug-drug interaction, metabolite formation, drug toxicity and ADME profile of a hit. Drug-induced liver injury is the most frequent reason for the withdrawal of an approved drug from the market and hepatocytes have a central role in the metabolism of xenobiotics. Cytotoxicity screening assays can also give some information about toxicity early drug discovery process. A set of goals in lead compound selection must be shared between all areas involved so the chances of success can be improved in translational research.
Keywords: Toxicity screening, lead compound, parasitic diseases, drug discovery
Current Drug Targets
Title: Early Toxicity Screening and Selection of Lead Compounds for Parasitic Diseases
Volume: 10 Issue: 3
Author(s): Renata Campos Nogueira, Jose Fernando Oliveira-Costa, Matheus Santos de Sa, Ricardo Ribeiro dos Santos and Milena Botelho Pereira Soares
Affiliation:
Keywords: Toxicity screening, lead compound, parasitic diseases, drug discovery
Abstract: Despite many advances made in disease mechanisms knowledge and drug discovery and development processes, the election of promising lead compounds continues to be a challenge. Efficient techniques are required for lead selection of hit compounds selected through in vitro pharmacological studies, in order to generate precise low cost throughput data with minimal amount of compound to support the right decision making. In this context, the selection of lead compounds with physicochemical parameters that will benefit orally bioavailable drugs are crucial for patients compliance and cost effectiveness, as well as for successful pharmacology. A concept based in Lipinskis rules point out the importance of analyzing these informations in early stages. A hepatocyte screening system may provide data on many processes such as drug-drug interaction, metabolite formation, drug toxicity and ADME profile of a hit. Drug-induced liver injury is the most frequent reason for the withdrawal of an approved drug from the market and hepatocytes have a central role in the metabolism of xenobiotics. Cytotoxicity screening assays can also give some information about toxicity early drug discovery process. A set of goals in lead compound selection must be shared between all areas involved so the chances of success can be improved in translational research.
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Nogueira Campos Renata, Oliveira-Costa Fernando Jose, de Sa Santos Matheus, dos Santos Ribeiro Ricardo and Soares Botelho Pereira Milena, Early Toxicity Screening and Selection of Lead Compounds for Parasitic Diseases, Current Drug Targets 2009; 10 (3) . https://dx.doi.org/10.2174/138945009787581212
DOI https://dx.doi.org/10.2174/138945009787581212 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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