Lhasa Ltd

DEREK for LHASA Ltd. Knowledge-Based Systems www.lhasalimited.org Mutagenicity, carcinogenicity,... 

Several expert systems have been developed for the prediction of chemical fate within organisms, or primarily metabolism. Three of the best known are META (Klopman et al., 1994 Talafous et al., 1994), MetabolExpert (Darvas et al 1999) initiated as a research project by CompuDrug in 1985, and a more recent program METEOR (LHASA Ltd., University of Leeds, U.K.). A formal comparison of the predictions of these systems does not appear to have been performed and published, although the predictions of META, MetabolExpert, and several human experts for a drug were presented for comparative purposes (Wilbury, 1999). 

The METEOR expert system, first marketed in 1999, is a newer development than MetabolExpert or META. It provides qualitative predictions of metabolic fate in mammals and the likelihood of individual biotransformations. The system, developed and marketed by LHASA Ltd., evolved out... 

I thank Dr. Anthony Long and my other colleagues at LHASA Ltd for their advice and assistance with this review. Thanks are also due to Dr. Mark Cronin, Liverpool John Moores University, for reviewing the manuscript and giving encouragement throughout. 

The computational toxicology software programs and models were obtained by FDA/CDER/ICSAS through cooperative research and development agreements with MDL Information Systems and Lhasa Ltd (Benz, 2007)... 

Lhasa Ltd., School of Chemistry, University of Leeds, Leeds, UK. URL http //www.chem. leeds.ac.uk/LUK/derek/index.html. 

In silico tools make a significant contribution to the SAR-based early identification of potential toxicity. An increasing volume of published preclinical and clinical toxicity data are collected and used to build structure-related searchable databases. These expert knowledge databases can analyze chemical structures and match them with potential mechanisms of toxicity. DEREK for Windows (Lhasa Ltd.)39 is one of such broadly used knowledge-based expert systems to provide toxicology alerts for new compounds. Although certainly not comprehensive, numerous efforts have been made to predict hepatotoxicity. Recently,... 

Lhasa Ltd, DEREK, https //www.lhasalimited.org/index.php/derek/ Accessed 08. 05. 

Another program available form Lhasa Ltd. is Meteor, software that allows predicting metabolic pathways of xenobiotic compounds [13-15], Again, the program uses expert knowledge in form of rules to predict the metabolic pathway of compounds. The predictions are presented in metabolic trees, similar to a synthesis tree, and may be filtered according to the likelihood of metabolites. 

DEREK (Deductive Estimation of Risk from Existing Knowledge Lhasa Ltd, Leeds, UK) is a rule-based system, which examines toxicity effects of potential drugs. 

Souree ACD/ Labs Simulations Plus, Inc. Multicase Inc. Lhasa Ltd. GeneX- plain GeneX- plain Optib- rium. Ltd. Accelerys... 

LHASA, UK, Ltd. School of Chemistry University of Leeds Leeds, LS2 9JT, U.K. 

Fig. 9.9. Computer screen from the LHASA program showing a reaction step (with permission of LHASA UK Ltd). 

The primary purpose of a reaction database system is to provide quick and easy access to the reaction literature. Users of synthesis planning programs have a need for such access to the literature in elaborating routes suggested by an analysis. An interface between LHASA and ORAC has recently been developed to provide such a link. The interface allows literature precedents for synthetic steps proposed by LHASA to be retrieved automatically from ORAC s database of over 120,000 reactions and to be displayed to the user on an ORAC Display Form. Company databases can also be accessed to search and display in-house preparative methods and processes in conjunction with databases supplied by ORAC Ltd. 

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