Toxicology Strategies for Drug Discovery - Present and Future: Introduction

Humphreys, W. Griffith; Will, Yvonne; Guengerich, F. Peter

doi:10.1021/acs.chemrestox.6b00049

Cited by 4 publications

(2 citation statements)

References 6 publications

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“…Moreover, drug delivery of substances to the brain has an important role in the discovery and development of new central nervous system disease treatments [70]. The most important challenge 2021 -European Journal of Chemistry -CC BY NC -DOI: 10.5155/eurjchem.12.4.488-492.2152 is the efficacy and safety, which it should address with an issue in their security and that there is no biotoxicity during drug design and development [69,71]. Zebrafish model is a vertebral animal model with complex brains and behaviors similar to humans that allows statistical reliability, feasibility for modification, and more stringent regulation.…”

Section: The Use Of Zebrafish To Toxicological Evaluationsmentioning

confidence: 99%

The use of zebrafish to evaluate neuropharmacology of the gold nanoparticles

Montes

2021

Eur J Chem

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Zebrafish (Danio rerio) is a vertebrate animal used in animal model research with complex brains and behaviors similar to humans and associate with low coast become a model attractive for the academic community to seek zebrafish for scientific research. Studies on diseases of the central nervous system (CNS) have advanced and news therapeutic agents were developed for treatment these disorders. Reports suggest that the zebrafish model supports the neurodegenerative studies due functional conservation between human genes implicated in neurodegenerative disorders. The discovery of therapeutic compounds for CNS using the zebrafish model allows to show a neuroprotective action or neurotoxicity that might alter the behavioral changes. Neurotoxicity tests might perform in zebrafish’s embryos into 96 multi-well plates, which reduces the amount of substances used and cost. The bioactive compounds able to penetrate the blood-brain barrier (BBB) have important role physicochemical properties that might be desirable pharmacological effects and zebrafish trials allow if the substances might penetrate BBB and to exert central activity. The assays zebrafish are used to analyze nanoparticles that are small molecules used to explore variety applications in human health. Gold nanoparticles (AuNPs) has important properties which are extremely interest for pharmaceutical area such as drug delivery, cellular imaging, diagnostics, and therapeutic agents. Gold nanoparticles enhances Parkinson symptoms and improved neuroinflammation. Some studies show zebrafish might use to evaluate gold nanoparticles for human health hazard and toxicity studies. There is enormous potential for zebrafish in preclinical assays due to predict pharmacological and toxicity effects. Specific guidelines focused on methodologies in the zebrafish are needed to ensure adequate reproducible trials.

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Section: The Use Of Zebrafish To Toxicological Evaluationsmentioning

confidence: 99%

The use of zebrafish to evaluate neuropharmacology of the gold nanoparticles

Montes

2021

Eur J Chem

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“…The expertise rely on on various aspects of drugs viz. genetic toxicity, evolutionary relationship, chemical features, quantitative statistical probabilities, sensitivity, specificity and other measures obtained through computational models (Valerio 2011;Humphreys et al 2016). Similarly, the ICH guidelines monitors various safety aspects for carcinogenicity, genotoxicity and reprotoxicity testing in animals.…”

Section: The Way Aheadmentioning

confidence: 99%

A multiparametric organ toxicity predictor for drug discovery

Patel

Kumar

Rawal

et al. 2019

Toxicology Mechanisms and Methods

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The assessment of major organ toxicities through in silico predictive models plays a crucial role in drug discovery. Computational tools can predict chemical toxicities using the knowledge gained from experimental studies which drastically reduces the attrition rate of compounds during drug discovery and developmental stages. The purpose of in silico predictions for drug leads and anticipating toxicological endpoints of absorption, distribution, metabolism, excretion and toxicity, clinical adverse impacts and metabolism of pharmaceutically active substances has gained widespread acceptance in academia and pharmaceutical industries. With unrestricted accessibility to powerful biomarkers, researchers have an opportunity to contemplate the most accurate predictive scores to evaluate drug's adverse impact on various organs.A multiparametric model involving physico-chemical properties, quantitative structure-activity relationship predictions and docking score was found to be a more reliable predictor for estimating chemical toxicities with potential to reflect atomic-level insights. These in silico models provide informed decisions to carry out in vitro and in vivo studies and subsequently confirms the molecules clues deciphering the cytotoxicity, pharmacokinetics, and pharmacodynamics and organ toxicity properties of compounds. Even though the drugs withdrawn by USFDA at later phases of drug discovery which should have passed all the state-of-the-art experimental approaches and currently acceptable toxicity filters, there is a dire need to interconnect all these molecular key properties to enhance our knowledge and guide in the identification of leads to drug optimization phases. Current computational tools can predict ADMET and organ toxicities based on pharmacophore fingerprint, toxicophores and advanced machine-learning techniques.

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Investigating the link between drug metabolism and toxicity

Humphreys¹

2023

Overcoming Obstacles in Drug Discovery and Development

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Toxicology Strategies for Drug Discovery - Present and Future: Introduction

Cited by 4 publications

References 6 publications

The use of zebrafish to evaluate neuropharmacology of the gold nanoparticles

The use of zebrafish to evaluate neuropharmacology of the gold nanoparticles

A multiparametric organ toxicity predictor for drug discovery

Investigating the link between drug metabolism and toxicity

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