Derek Nexus 

Consultancy Report 

CONFIDENTIAL 

ForthTox Limited 

PO Box 13550, Linlithgow, West Lothian, EH49 7YU, U.K. 

Telephone +44 (0)1506-844036 

www.forthtox.com Page 1 of 8 

Toxicological Analysis of using 

Derek Nexus

Prepared for: 

Date of report: 11 September 2012 

ForthTox report ref: CSI001drk 
 

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The Derek Nexus System 

The Derek Nexus system has been designed for the qualitative prediction of the possible 

toxicity of chemicals. The predictions made by Derek Nexus are intended as an aid to 

toxicological assessment and, where appropriate, should be used in conjunction with other 

methods. The absence of Derek Nexus predictions for any given compound in no way 

implies that the compound is, or is expected to be, non-toxic. 

Disclaimer 

Lhasa Limited make no warranties, expressed or implied, with respect to Derek Nexus or the 

output thereof. In particular, but without limitation, Lhasa Limited make no representation or 

warranty of merchantability or of fitness for any specific purpose of use. In no event shall 

Lhasa Limited be liable for any consequential or incidental damages arising from or relating 

to, the use of Derek Nexus or the output thereof. 

Lhasa Limited 

22-23 Blenheim Terrace 

Woodhouse Lane 

Leeds LS2 9HD UKx

Tel: +44 (0)113 394 6020 

Fax: +44 (0)113 394 6099 

E-mail: info@lhasalimited.org
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Derek Nexus 

Consultancy Report 

Toxicological Analysis of usmg 

Derek Nexus 

Date of analysis:	 16th July 2012 

Program version:	 Derek Nexus 2.0.3 

ForthTox report ref:	 CSIOOI drk 

Personnel responsible 

Structure entry, 0 R Woolley PhD, BSc, MSB, CBiol 

processing and reporting European Registered Toxicologist 

Report review	 A P A H Woolley MSc, DABT, FRCPath, ERT
 

European Registered Toxicologist
 

This report has been generated from output from Derek Nexus 2.0.3, using the structure 

illustrated and the processing constraints and endpoints described. 

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Introduction 

 was evaluated for multiple toxicological endpoints in 

a range of mammalian and bacterial species using Derek Nexus.

The following structures, copied from the Derek output, were processed:

Protocol adopted for processing 

Knowledge base version: 11_16_07_2012 

Species: Escherichia coli, Salmonella typhimurium, bacterium, dog, 

guinea pig, hamster, human, mammal, monkey, mouse, 

primate, rabbit, rat and rodent

Endpoints searched: Carcinogenicity, Chromosome damage, Genotoxicity, HERG 

channel inhibition, Hepatotoxicity, Irritation, Miscellaneous 

endpoints, Mutagenicity, Ocular toxicity, Rapid prototypes: 

bladder disorders, Rapid prototypes: blood in urine, Rapid 

prototypes: bone marrow toxicity, Rapid prototypes: 

bradycardia, Rapid prototypes: chromosome damage in vitro, 

Rapid prototypes: hepatotoxicity, Rapid prototypes: kidney 

disorders, Rapid prototypes: mitochondrial dysfunction, Rapid 

prototypes: nephrotoxicity, Rapid prototypes: splenotoxicity, 
 

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Rapid prototypes: thyroid toxicity, Reproductive toxicity, 

Respiratory sensitisation, Skin sensitisation, Thyroid toxicity

Processing constraints: The option to perceive tautomers was selected.

Rapid prototype alerts are typically developed within the Derek knowledge base to describe 

initial classes of structures associated with toxicological effects identified from a large 

dataset. They have a specific scope and limited comments but do not contain references or 

examples. They are useful as an indication of a potential toxicophore. 

Result 

 

Nothing to report 

Comment and discussion 

Derek Nexus assigns various levels of non-numeric likelihood to its predictions ranging from 

CERTAIN to CONTRADICTED, via PROBABLE, PLAUSIBLE, EQUIVOCAL, 

DOUBTED, IMPROBABLE, IMPOSSIBLE and OPEN. In the Derek lexicon, PLAUSIBLE 

indicates that the structure has activated an alert for the endpoint in question. There is 

sufficient information in the database to support the prediction. EQUIVOCAL – indicates 

that there is an equal weight of evidence for and against the proposition. OPEN – means that 

there is no evidence that supports or opposes the proposition. 

 was evaluated for multiple toxicological endpoints in 

a range of mammalian and bacterial species using Derek Nexus. No alerts were triggered by 

this structure. Furthermore, it is likely that the boron will not be available to cause toxicity as 

it is covalently bound to the oxygen molecules and thus is likely be sterically shielded and 

hindered.

Derek Nexus has been accepted by regulatory agencies such as the FDA and the EMEA for 

the prediction of the genotoxicity of pharmaceutical impurities. The accuracy of Derek for 

Windows has been assessed in a number of publications. 

Derek for Windows (DfW; the predecessor of Derek Nexus) is considered to be reliably 

predictive of mutagenicity, carcinogenicity and, to a lesser extent, genotoxicity (based in part 

on the number of alerts for each in the software) [Dearden (2003), Hulzebos (2003) Hayashi 

et al (2005) and Snyder et al (2004)]. 
 

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Hulzebos and Posthumus R (2003) reported that DfW correctly categorised 90% of the 

chemicals in chemical classes, while 10% of the structural fragments needed a more detailed 

description. The accuracy of prediction was around 75% for genotoxicity and carcinogenicity 

for a limited number of chemicals. Irritation and reproductive toxicity were predicted poorly. 

It should be noted that this review was conducted using an earlier version of DfW (version 5) 

and that considerable development of the software has taken place since then, in the form of 

annual updates. 

Snyder assessed DfW 5 and two other commonly used computer databases, using information 

for 394 marketed pharmaceuticals with Ames Salmonella reversion assay and other genetic 

toxicology findings extracted from the 2000–2002 Physicians’Desk Reference. They reported that 

Derek for Windows gave the following results for the Ames test: 

Sensitivity: 14/27 (51.9%) 

Specificity: 260/346 (75.1%) 

Concordance: 274/372 (73.6%) 

To a certain extent, the results of such comparisons are dependent on the database used for 

the validation comparisons. 

Hillebrecht et al (2011) comparatively evaluated several in silico systems for Ames test 

mutagenicity prediction, including Derek and Leadscope. They used a database purchased 

from Leadscope, a set of chemicals taken from a recent publication by Hansen, purged of 

chemicals common to the Leadscope data, and a set of chemicals from proprietary data held 

by Hoffmann-La Roche. The results from the Roche data set were said to be skewed by the 

high ratio of negative to positive chemicals in the data compared (6.78) to that for the other 

two sets (1.27 for Leadscope and 0.49 for the Hansen set). This work was based on the use of 

9681 compounds of which a quarter were proprietary pharmaceutical compounds. Derek 

showed good sensitivity (approximately 70%) and specificity (approximately 78% for the 

Leadscope database and 62% for the Hansen chemicals). 

Negative predictions of mutagenicity by such software have been accepted as indicating the 

absence of a structural alert and that no further toxicological investigation would be 

necessary. 

Using DfW (the predecessor of Derek Nexus) a review of a guinea pig archive data for 

compounds eliciting allergic contact dermatitis and a local lymph node assay (LLNA) data 

set was conducted. DfW correctly predicted 82.9% and 73% of the results from the guinea 

pig and LLNA data (Fedorowicz et al., 2005). 
 

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Conclusion 

In conclusion, was evaluated for multiple toxicological 

endpoints in a range of mammalian and bacterial species using Derek Nexus. No alerts were 

triggered by this structure. Furthermore, it is likely that the boron will not be available to 

cause toxicity as it is covalently bound to the oxygen molecules and thus is likely be 

sterically shielded and hindered.
 

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References used by DEREK:

None. 

References used by ForthTox:

Dearden, J.C. (2003). In silico prediction of drug toxicity. Journal of Computer-Aided 

Molecular Design 17,119–127. 

Fedorowicz, A., Singh, H., Soderholm. S. & Demchuk, E. (2005) Structure-activity models 

for contact sensitization. Chem Res Toxicol. 18(6). pp 954-69. 

Hayashi, M., Kamata, E., Hirose, A., Takahashi, M., Morita, T. and Ema, M. (2005). In silico 

assessment of chemical mutagenesis in comparison with results of Salmonella microsome 

assay on 909 chemicals. Mutation Research 588 129–135. 

Hillebrecht A, Muster W, Brigo A, Kansy M, Weiser T and Singer T (2011). Comparative 

evaluation of in silico systems for Ames test mutagenicity prediction: scope and limitations. 

Chemical Research in Toxicology 24, 843-54. 

Hulzebos, E.M. and Posthumus, R. (2003): (Q)SARS: Gatekeepers against risk on chemicals? 

SAR and QSAR in Environmental Research, 14 (4), 285–316. 

Snyder RD, Pearl GS, Mandakas G, Choy WN, Goodsaid F, Rosenblum IY. (2004) 

Assessment of the sensitivity of the computational programs DEREK, TOPKAT, and 

MCASE in the prediction of the genotoxicity of pharmaceutical molecules. Environ Mol 

Mutagen. 43(3), 143-58.