scholarly journals Zebrafish: an emerging technology for in vivo pharmacological assessment to identify potential safety liabilities in early drug discovery

2008 ◽  
Vol 154 (7) ◽  
pp. 1400-1413 ◽  
Author(s):  
T P Barros ◽  
W K Alderton ◽  
H M Reynolds ◽  
A G Roach ◽  
S Berghmans
Keyword(s):  
Drug Discovery ◽  
Emerging Technology ◽  
Potential Safety ◽  
Early Drug

scholarly journals An Ultrafast and Flexible LC-MS/MS System Paves the Way for Machine Learning Driven Sample Processing and Data Evaluation in Early Drug Discovery

2021 ◽  
Author(s):  
Tim Häbe ◽  
Christian Späth ◽  
Steffen Schrade ◽  
Wolfgang Jörg ◽  
Roderich Süssmuth ◽  
...  
Keyword(s):  
Machine Learning ◽  
Decision Making ◽  
Drug Discovery ◽  
Data Evaluation ◽  
In Vivo Studies ◽  
Integrated Analysis ◽  
Limit Of Quantitation ◽  
Early Drug ◽  
The Way

Rationale: Low speed and flexibility of most LC-MS/MS approaches in early drug discovery delays sample analysis from routine in vivo studies within the same day of measurements. A highthroughput platform for the rapid quantification of drug compounds in various in vivo assays was developed and established in routine bioanalysis. Methods: Automated selection of an efficient and adequate LC method was realized by autonomous sample qualification for ultrafast batch gradients (9 s/sample) or for fast linear gradients (45 s/sample) if samples require chromatography. The hardware and software components of our Rapid and Integrated Analysis System (RIAS) were streamlined for increased analytical throughput via state-of-the-art automation while keeping high analytical quality. Results: Online decision-making was based on a quick assay suitability test (AST) based on a small and dedicated sample set evaluated by two different strategies. 84% of the acquired data points were within ±30% accuracy and 93% of the deviations between the lower limit of quantitation (LLOQ) values were ≤2-fold compared to standard LC-MS/MS systems while speed, flexibility and overall automation was significantly improved. Conclusions: The developed platform provided an analysis time of only 10 min (batch-mode) and 50 min (gradient-mode) per standard pharmacokinetic (PK) study (62 injections). Automation, data evaluation and results handling were optimized to pave the way for machine learning based decision-making regarding the evaluation strategy of the AST

scholarly journals Erratum to the paper: In vitro membrane binding and protein binding (IAM MB/PB technology) to estimate in vivo distribution: applications in early drug discovery

ADMET & DMPK ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 267-268
Author(s):  
Klara Livia Valko ◽  
Simon Teague ◽  
Charles Pudgeon
Keyword(s):  
Drug Discovery ◽  
Protein Binding ◽  
Membrane Binding ◽  
In Vivo Distribution ◽  
Early Drug

The authors of the original paper published with the same title: ADMET & DMPK 5(1) (2017) 14-38; doi: 10.5599/admet.5.1.373, apologize for the error in the plot on Figure 5. The erratum gives a correct plot.

scholarly journals Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research

Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 641
Author(s):  
Elisa Rampacci ◽  
Valentina Stefanetti ◽  
Fabrizio Passamonti ◽  
Marcela Henao-Tamayo
Keyword(s):  
Drug Discovery ◽  
Vaccine Development ◽  
Nontuberculous Mycobacteria ◽  
Critical Role ◽  
Developed Countries ◽  
Alternative Methods ◽  
In Vivo Models ◽  
Early Drug

Nontuberculous mycobacteria (NTM) represent an increasingly prevalent etiology of soft tissue infections in animals and humans. NTM are widely distributed in the environment and while, for the most part, they behave as saprophytic organisms, in certain situations, they can be pathogenic, so much so that the incidence of NTM infections has surpassed that of Mycobacterium tuberculosis in developed countries. As a result, a growing body of the literature has focused attention on the critical role that drug susceptibility tests and infection models play in the design of appropriate therapeutic strategies against NTM diseases. This paper is an overview of the in vitro and in vivo models of NTM infection employed in the preclinical phase for early drug discovery and vaccine development. It summarizes alternative methods, not fully explored, for the characterization of anti-mycobacterial compounds.

Zebrafish based assays for the assessment of cardiac, visual and gut function — potential safety screens for early drug discovery

2008 ◽  
Vol 58 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Stéphane Berghmans ◽  
Paul Butler ◽  
Paul Goldsmith ◽  
Gareth Waldron ◽  
Iain Gardner ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Potential Safety ◽  
Gut Function ◽  
Function Potential ◽  
Early Drug

scholarly journals Zebrafish: An Attractive Model to Study Staphylococcus aureus Infection and Its Use as a Drug Discovery Tool

2021 ◽  
Vol 14 (6) ◽  
pp. 594
Author(s):  
Sari Rasheed ◽  
Franziska Fries ◽  
Rolf Müller ◽  
Jennifer Herrmann
Keyword(s):  
Drug Discovery ◽  
High Throughput Screening ◽  
Academic Research ◽  
Aureus Infection ◽  
Frequency Of Use ◽  
Toxicological Studies ◽  
Infection Models ◽  
Vertebrate Model ◽  
Early Drug

Non-mammalian in vivo disease models are particularly popular in early drug discovery. Zebrafish (Danio rerio) is an attractive vertebrate model, the success of which is driven by several advantages, such as the optical transparency of larvae, the small and completely sequenced genome, the small size of embryos and larvae enabling high-throughput screening, and low costs. In this review, we highlight zebrafish models of Staphyloccoccus aureus infection, which are used in drug discovery and for studying disease pathogenesis and virulence. Further, these infection models are discussed in the context of other relevant zebrafish models for pharmacological and toxicological studies as part of early drug profiling. In addition, we examine key differences to commonly applied models of S. aureus infection based on invertebrate organisms, and we compare their frequency of use in academic research covering the period of January 2011 to January 2021.

A modern in vivo pharmacokinetic paradigm: combining snapshot, rapid and full PK approaches to optimize and expedite early drug discovery

2013 ◽  
Vol 18 (1-2) ◽  
pp. 71-78 ◽  
Author(s):  
Chun Li ◽  
Bo Liu ◽  
Jonathan Chang ◽  
Todd Groessl ◽  
Matthew Zimmerman ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Early Drug

scholarly journals Chromatographic technique to support ADMET&DMPK in early drug discovery

ADMET & DMPK ◽  
2018 ◽  
Vol 6 (2) ◽  
pp. 71-73 ◽  
Author(s):  
Klara Livia Valko
Keyword(s):  
Drug Discovery ◽  
New Technologies ◽  
Animal Experiments ◽  
Chromatographic Technique ◽  
Drug Discovery Process ◽  
Structure And Property ◽  
Drug Molecules ◽  
Site Of Action ◽  
Early Drug

The drug discovery process usually involves the discovery of a potent new chemical entity which has shown some activity on a target that is believed to be relevant in a certain type of disease. However, the structure and property of these putative drug molecules may have to be modified in order to ensure that they are able to exert the desired in vivo pharmacological effect. The candidate molecules usually have to be absorbed from the gastrointestinal system and therefore they must show appropriate solubility and permeability to be able to reach the target enzyme in vivo with a sufficient free biophase concentration at the site of action. This means that the physicochemical properties and the protein and phospholipid binding has to be optimized in order to achieve the desired in vivo ADMET and DMPK profile. The ADME studies usually require animal experiments or the use of biological samples, for example tissues which is expensive and involves time-consuming procedures. New technologies and approaches can accelerate this process.

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