In similarity search mode, MPM identifies candidate targets by comparing gene expression profiles generated with the investigational drug to a library of profiles compiled from various sources such as FDA-approved drugs, investigational compounds, knock-down siRNA experiments and knock-in studies as well as a large number of gene expression profiles comprising the most common malignancies. The algorithm generates a list of drugs with known molecular targets that most closely resemble the targets underlying the mechanism of action of the new chemical entity, based on the high similarity between the sets of expressed genes. Literature searches are used to further refine the list of possible targets and to generate a small set of investigational targets. These are then validated experimentally using RNA interference technology and routine molecular biology techniques.

 

In phenotype reverse mode, MPM searches for disease states whose gene expression profiles are complementary to the expression profile generated by the NCE under investigation. At the molecular level, disease states are characterized by genes that are over- or under-expressed relative to a ‘healthy’ reference control. Effective drugs have the ability to reverse these patterns thus providing a cure for the cellular disturbance that triggered the abnormal gene expression. To identify disease targets for an investigational drug, MPM compares gene expression patterns obtained with the drug to a library of gene expression patterns representing the complementary profiles of the gene sets characterizing disease states. The initial list of possible disease indications is then further refined by a close examination of the networks of genes targeted by the investigational drug. Apart from rapidly identifying disease targets for new drugs, MPM can also be employed to re-profile or re-position existing drugs and thus help generate a new round of patents. As an additional benefit, MPM can help identify the most effective combination therapies for a given disease.

 

We use a combination of both classical as well as state of the art reagents and technniques, such as RNA interference to validate the predicted targets for small molecules.

 

instrumentation


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Canada Dr.Serban San-Marina

Europe Dr.Iosif Ionel

 

The Molecular Profile Matcher Platform

The Molecular Profile Matcher (MPM) is a suite of proprietary software that speeds up the process of target identification, assists in drug re-profiling and helps select effective drug combinations. MPM can operate in similarity search mode or in reverse phenotype mode.

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