The Role of Alternative Toxicological Trials in Drug Discovery Programs. The Case of Caenorhabditis elegans and Other Methods

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The discovery of a new drug requires over a billion dollars and around 12 years of research efforts, and toxicity is the leading reason for the failure to approve candidate drugs. Many alternative methods have been validated to detect toxicity as early as possible to diminish the waste of resources and efforts in medicinal chemistry research, and in vivo alternative methods are especially valuable for the amount of information they can provide at little cost and in a short time. In this work, we present a review of the literature published between the years 2000 and 2021 on in vivo alternative methods of toxicity screening employed in medicinal chemistry, which we believe will be useful because, in addition to shortening the research time, these studies provide much additional information aside from the toxicity of drug candidate compounds. These in vivo models include zebrafish, Artemia salina, Galleria mellonella, Drosophila melanogaster, planarians, and Caenorhabditis elegans. The most published ones in the last decade were zebrafish, D. melanogaster, and C. elegans due to their reliability, ease, and cost-effectiveness in implementation and flexibility. Special attention is given to C. elegans because of its rising popularity, a wide range of uses, including toxicity screening, and active effects measurement, from antioxidant effects to anthelmintic and antimicrobial activities, and its fast and reliable results. Over time, C. elegans also became a viable high-throughput (HTS) automated drug screening option. Additionally, this manuscript lists briefly the other screening methods used for the initial toxicological analyses and the role of alternative in vivo methods in these scenarios, classifying them as in silico, in vitro and alternative in vivo models that have been receiving a growing increase in interest in recent years.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:29

Enthalten in:

Current medicinal chemistry - 29(2022), 32 vom: 31., Seite 5270-5288

Sprache:

Englisch

Beteiligte Personen:

Göethel, Gabriela [VerfasserIn]
Augsten, Lucas Volnei [VerfasserIn]
das Neves, Gustavo Machado [VerfasserIn]
Gonçalves, Itamar Luís [VerfasserIn]
de Souza, João Pedro Silveira [VerfasserIn]
Garcia, Solange Cristina [VerfasserIn]
Eifler-Lima, Vera Lucia [VerfasserIn]

Links:

Volltext

Themen:

Alternative models
Antioxidants
Caenorhabditis elegans
Drug development
Drug discovery
Journal Article
Medicinal chemistry
Review
Toxicity screening
Toxicology trials

Anmerkungen:

Date Completed 19.09.2022

Date Revised 19.09.2022

published: Print

Citation Status MEDLINE

doi:

10.2174/0929867329666220329190825

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM338827137