Malaria Kinase Inhibitors

Summary

The kinase family is one of the most important anti-cancer targets of the pharmaceutical industries. With more than 500 members in human, they appear as the most validated target in oncology due to their important role in cell cycle, proliferation survival and apoptosis. Most pharmaceutical industries with oncology unit have kinase plateform to help in developing specific compounds. The goal of this project is to use this knowledge obtained on anti-kinase inhibitors to develop therapies against kinases inside parasite, in particular plasmodium falciparum.

Indeed, kinases play an important role in every stages of the parasites life cycle, from asexual proliferation of the parasite within the host cell to its sexual development of the gametocytes and its transmission to the transmitter, e.g. the female mosquito for malaria. We are using a new chemoinformatics approach based on fragments library to develop adapted chemical scaffold libraries specific for anti-parasite kinome.

Structural Chemogenomics Approach:

The vast amount of knowledge has been gathered concerning the kinase family: more than 3000 structures have been solved by X-Ray crystallography and large amount of compounds has been tested biochemically towards those kinases. We are using a chemo-proteomic approach to select the adequate human anti-kinases inhibitors to target the corresponding plasmodium kinase. The first step consists in the structural classification of the human kinase binding site (to be published).

Publication Sup'Biotech

  • Enzyme classification using 3D signatures of protein binding sites Ahmed EL HAMADI1, Joël MOUTOUSSAMY, Edwin CARLINET AND Jean-Yves TROSSET. Journée Biologie Informatiques et Mathématiques. Cahiers du JOBIM. Institut Pasteur, 28 Juin 2011.

Lab Internal

FLO +

FLO+ : is a drug design and virtual screening software to study protein ligand interactions

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Jean-Yves Trosset