Learning rules for comparing the activities of Alzheimer's drugs

Contents and links

Introduction: Alzheimer's disease

Alzheimer's disease has long been recognised as one of the most disabling conditions affecting the aged. It is the major cause of dementia among elderly people. The drug Tacrine has drawn considerable attention because of a report of its clinical efficacy for this problem. Its structure is shown here:

However, large-scale clinical trials show that the primary disadvantage of Tacrine is its high toxicity. This has led to investigations into possible variants of the basic Tacrine structure. Some reported variations used the following structure

In this structure, new compounds are created by substituting for R and X, where the substitution for X can be in position 6 or 7.

The need to guide experimentation

The literature contains many reports of tests on the properties of new drugs - in the case of Alzheimer's, desirable proprties include However, these reports do not indicate any particular pattern followed in creating these new drugs. The aim of our research is to learn rules that tell us what makes a drug have a desirable property (for example, low toxicity). Hopefully, these rules will offer better guidance for the synthesis of new drugs.

Using ILP to learn drug properties

In our experiments, data from the chemical literature was converted into a representation suitable for ILP, as described in [King, R.D., Srinivasan, A. and Sternberg, M.J.E.(1995)]. The chemical data itself is taken from [Shutske G.M. et al(1989)].

In the dataset provided here, rules are to be learnt for each property using the following information:

The Golem dataset

The data used in these experiments is contained in one compressed TAR file.


King, R.D., Srinivasan, A. and Sternberg, M.J.E. (1995).
Relating chemical activity to structure: an examination of ILP successes.
New Gen. Comput. (to appear).
Shutske G.M., Pierrat F.A., Kapples K.J., Cornfeldt M.L., Szewczak M.R., Huger F.P., Bores G.M., Haroutunian V. and Davis K.L. (1989).
9-Amino-1,2,3,4-tetrahydroacridin-1-ols: Synthesis and Evaluation as Potential Alzheimer's Disease Therapeutics.

Up to applications main page.

Machine Learning Group Home Page