Early toxicity screening and selection of lead compounds for parasitic diseases.
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 Lipinski's 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.
Nogueira
Renata Campos
RC
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil.
Oliveira-Costa
José Fernando
JF
de Sá
Matheus Santos
MS
dos Santos
Ricardo Ribeiro
RR
Soares
Milena Botelho Pereira
MB
D000818:Animals; D000977:Antiparasitic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D010272:Parasitic Diseases / Q000188:drug therapy*; D018675:Toxicity Tests
D000977:Antiparasitic Agents