The Development and Validation of Expert Systems for Predicting Toxicity

Dearden, John C.; Barratt, Martin D.; Benigni, Romualdo; Bristol, Douglas W.; Combes, Robert; Cronin, Mark; Judson, Philip N.; Payne, Martin; Richard, Ann M.; Tichý, M; Worth, Andrew; Yourick, Jeffrey J.

doi:10.1177/026119299702500303

Cited by 68 publications

(35 citation statements)

References 55 publications

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“…Furthermore, Optimum Prediction Space (OPS) validation method is utilized to assist in interpreting the results. Low confidence is assigned to a toxicity prediction that lies outside the OPS [48].…”

Section: In Silico Prediction Of Pharmacokinetics and Toxicity Propermentioning

confidence: 99%

<i>In Silico</i> Discovery of Natural Products Against Dengue RNA-Dependent RNA Polymerase Drug Target

Billones

Clavio

2021

CBIJ

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The viral infection caused by the dengue virus (DENV) is one of the most challenging diseases in the tropical regions of the world. The absence of drugs for dengue to this date calls for intense efforts to discover and develop the much coveted therapeutics for this mosquito-borne disease. One of the most attractive antiviral targets is the DENV RNAdependent RNA polymerase (RdRp), which catalyzes the de novo initiation as well as elongation of the flavivirus RNA genome. In this work, almost 5000 natural products were docked to DENV RdRp. The top 197 molecules with greater binding energies than the known ligand of the target were further clustered down to furnish 35 classes of molecular structures. These compounds with satisfactory predicted drug properties and with known natural origin can be further explored to pave the way for the first anti-dengue drug.

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Section: In Silico Prediction Of Pharmacokinetics and Toxicity Propermentioning

confidence: 99%

<i>In Silico</i> Discovery of Natural Products Against Dengue RNA-Dependent RNA Polymerase Drug Target

Billones

Clavio

2021

CBIJ

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“…COMPACT is a different system, which analyses the ability of a molecule to fit into the active site of the CYP1A1 isozyme (and some other CYP isozymes), by modelling molecular shape (planarity or area/depth) and chemical reactivity (covalent bond formation). The use of COMPACT is therefore limited to molecules that are activated by these CYP isozymes (151).…”

Section: Molecular and Qsar Modellingmentioning

confidence: 99%

“…The use of expert systemsExpert systems can be used either specifically or coupled with rule bases for predicting general toxicity(151,152). Examples of this include CASE and METACASE, HazardExpert and MetabolExpert, Derek for Windows and Meteor, as well as the TIMES metabolism simulator software(141, 153, 154; …”

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confidence: 99%

Metabolism: A Bottleneck inIn VitroToxicological Test Development

et al. 2006

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This is the 54th report of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). The main objective of ECVAM, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences, and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures that would enable it to become well informed about the state-of-the-art of non-animal test development and validation, and of opportunities for the possible incorporation of alternative methods into regulatory procedures. It was decided that this would be best achieved through a programme of ECVAM workshops, each addressing a specific topic, and at which selected groups of independent international experts would review the current status of various types of in vitro tests and their potential uses, and make recommendations about the best ways forward.A workshop on Metabolism: a bottleneck in in vitro toxicological test development, was held at

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“…Workshop 8 (the integrated use of alternatives for predicting toxicity) recommended that there should be a subsequent workshop focusing on the development and validation of computerised expert systems for predicting toxicity (8). This resulted in the organisation of workshop 24, on this topic, which was held in 1997 (24). Also, workshop 2 on phototoxicity testing identified a need for a test for phototoxic potential, and made suggestions for the development of in vitro assays for this endpoint (2).…”

Section: The Organisation Of Further Workhopsmentioning

confidence: 99%

The ECVAM Workshops: A Critical Assessment of their Impact on the Development, Validation and Acceptance of Alternative Methods

Combes

2002

Altern Lab Anim

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ECVAM initiated its workshop programme in 1994, to enable it to become well informed about the state of the art of non-animal test development and validation, and about the possible incorporation of alternatives into regulatory requirements for safety testing. Fifty-one such workshops had been held on specific topics, up to 2002. In these workshops, the current status of in vitro tests and their potential uses were reviewed and recommendations were made as to the best ways forward to progress and enhance the use of in vitro methods. Reports for 46 of these workshops have been published in ATLA. Most of the workshops focused on in vitro replacement methods, although an increasing number have dealt with reduction and refinement. The recommendations in the ECVAM workshops have been progressed further by: a) the formation of ECVAM task forces; b) the organisation of further workshops; c) the activities of scientific committees; d) the provision of earmarked research funding; and e) the conduct of validation studies. Examples of each of these activities are discussed. Some individual workshops are covered in more detail, and several recommendations that have so far not been acted on are also considered. The workshops and their reports have had a substantial effect on the development and implementation of alternative methods, and have been a major factor in contributing to the success of the first nine years of ECVAM's existence. It is strongly recommended that ECVAM continues to organise workshops and to publish their findings, and suggestions are made for topics for future workshops.

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The Development and Validation of Expert Systems for Predicting Toxicity

Cited by 68 publications

References 55 publications

<i>In Silico</i> Discovery of Natural Products Against Dengue RNA-Dependent RNA Polymerase Drug Target

<i>In Silico</i> Discovery of Natural Products Against Dengue RNA-Dependent RNA Polymerase Drug Target

Metabolism: A Bottleneck inIn VitroToxicological Test Development

The ECVAM Workshops: A Critical Assessment of their Impact on the Development, Validation and Acceptance of Alternative Methods

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