Derek Nexus

Derek Nexus is the expert, knowledge-based software that gives you accurate toxicity predictions quickly. Early, accurate in silico toxicity tests using Derek Nexus is the quick, inexpensive way to identify potentially toxic chemicals, aiding your experts in rejecting unsuitable drug candidates.

Expert, knowledge-based software that gives you accurate toxicity predictions quickly.

DEREK NEXUS

Why do you need Derek Nexus? 

General Approach

How Derek Nexus can be used

 

Features and Benefits

Negative Predictions

EC3 Predictions for Skin Sensitisation

Derek Knowledge Editor and Web Services 

 

Why do you need Derek Nexus?

Whether your industry is cosmetics, pharmaceuticals, chemicals, or you are in academia, Derek Nexus enables you to:

  • Evaluate the potential toxicity of existing or prospective chemicals.
  • Make decisions about which chemicals are likely to have ‘more favourable’ toxic profiles when you do not have all the experimental information you would like to have about the toxicity of each chemical.
  • Share internal toxicity data and knowledge with your colleagues by capturing it within Derek Nexus.
  • Improve the properties of a chemical in the R&D pipeline by slightly redesigning its molecular structure.
  • Save time and money by carrying out toxicity experiments on a large number of chemical candidates and selecting those with the most favourable outlook.
  • Learn using the extensive knowledge in the expert software as a toxicology training tool.

General Approach

When a structure is submitted to Derek Nexus, it is standardised and then compared to the certified Lhasa knowledge base and any custom knowledge bases that you have created using Derek Knowledge Editor, and a toxicity prediction is generated.

The Derek Nexus prediction includes an overall conclusion about the likelihood of toxicity of a structure and detailed reasoning information for the likelihood. The prediction is generated by applying expert knowledge rules in toxicology to the data returned from the knowledge base.

The structure standardisation in Nexus 2.2 uses a set of transform rules including, but not limited to, aromaticity perception, transforming pentavalent Nitrogens and removing specific stereochemistry. The aim of the standardisation is to interpret structures more accurately, in order to optimise predictions.

Endpoints

Derek Nexus predicts potential toxicity for most toxicological endpoints, including:

Derek Knowledge Base

The certified Derek knowledge base, created and supplied by Lhasa Limited, contains data from published sources and data donated by our member organisations. This data is collated, checked and verified by Lhasa scientists before being used to develop new knowledge rules and relationships. These rules and relationships are based on empirical observations that are supported by an understanding of the toxicity mechanism or by our rigorous, internal vetting process.

How Derek Nexus can be used

Derek Nexus is the expert, knowledge-based software that gives you accurate toxicity predictions quickly. Early, accurate in silico toxicity tests using Derek Nexus is the quick, inexpensive way to identify potentially toxic chemicals, aiding your experts in rejecting unsuitable drug candidates.

Derek Nexus has various uses, including:

  • Potential Mutagenic Impurities (PMI) Assessment and Management
  • As Part of a Defined Approach for Skin Sensitisation Assessment
  • Bacterial Mutagenicity Screening
  • 2-Stage Processing
  • Screening and Compound Profiling

Potential Mutagenic Impurities (PMI) Assessment and Management

Derek Nexus is widely used to assess PMIs and is used commonly within the pharmaceutical industry1 for the management of mutagenic impurities knowledge. Derek Nexus enables organisations to meet half of the requirements of ICH M7, and is supported further by:

  • Sarah Nexus; a statistical software for the prediction of mutagenicity
  • Vitic Nexus; holding a vast amount of relevant data
  • Mirabilis; expert and scientifically robust software for the calculation of purge factors of potentially mutagenic impurities in a synthetic route
  • Lhasa Carcinogenicity Database; a free, online database for the retrieval of relevant carcinogenicity data

Scientists use the tools in conjunction to perform read-across studies allowing users to make decisions across all available data.

As Part of a Defined Approach for Skin Sensitisation Assessment

There has been a significant drive to reduce, refine and replace animal models for the prediction of skin sensitisation. This is in part due to the implementation of EU regulation 1223/20092 which prohibits the sale and marketing of any cosmetics and cosmetic ingredients which have been tested on animals.

Derek Nexus predictions for skin sensitisations can be combined with in chemico/in vitro assays, in the form of a Defined Approach, to give a more accurate assessment of hazard3.

Click to enlarge

Figure 1: A simplified Defined Approach using Derek Nexus and a 2 out of 3 in silico/in chemico/in vitro method. 


Bacterial Mutagenicity Screening

In silico screening using Derek Nexus provides an early indication of potential mutagenic compounds and therefore reduces late stage attrition due to unforeseen toxicity4.

2-Stage Processing (Figure 1)

Various Derek Nexus users operate a 2-stage process. Stage 1 involves reviewing the high-level overview and stage 2 involves delving further into the details. In practice, this means that users can start with a simple prediction of potential toxicity, and if further information is required, users can interrogate the expert summary which contains additional material.

Figure 1: The 2-stage processing method using Derek Nexus


Screening & Compound Profiling

The transparency of predictions within Derek Nexus allows for data analysis, to prioritise lead series of compounds. Derek Nexus is designed with this workflow in mind, allowing:

  • Toxicity predictions for thousands of compounds for prioritisation for future development.
  • Detailed analysis of individual or multiple compounds facilitating decision making.

In each case, Derek Nexus provides the breadth and depth of information required.

References

  1. Dobo et al. (2012) ‘In silico methods combined with expert knowledge rule out mutagenic potential of pharmaceutical impurities: An industry survey’, Regulatory Toxicology and Pharmacology, vol. 62, no. 3, April, pp.449-455. http://dx.doi.org/10.1016/j.yrtph.2012.01.007
  2. European Union. (2013) Off. J. Eur. Union 56, 34–66
  3. Macmillan et al. (in press)
  4. Escobar et al. (2013) ‘Bacterial mutagenicity screening in the pharmaceutical industry’, Mutation Research, vol. 752, no. 2, April-June, pp.99-118. http://dx.doi.org/10.1016/j.mrrev.2012.12.002

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