WP2 is carried out by Dr. Laurent Meijer from the Roscoff Marine Biology lab, and Dr. Conrad Kunick from the Technische Universität Braunschweig. WP2 will attempt to identify, optimize and characterize small molecular weight pharmacological inhibitors specific to novel Leishmania protein kinases identified by this consortium (partner 1 and 5). Inhibition of these kinases should lead to compromised Leishmania propagation and survival in experimental infection models (partner 6), and, on a long-term basis, to the absence of toxicity for the human host. Reaching this aim involves the careful selection of essential parasite kinase genes (partners of WP5 and WP6), their cloning and expression in vectors suitable for high level expression of active recombinant kinases amenable to simple, semi-high throughput assays and protein crystallization (partners 1, 4 and 5). Following extensive screening of high chemical diversity libraries by in vitro kinase assay and in situ on macrophages infected with fluorescent parasites (partners 1 and 2), inhibitory hits will be optimized in terms of efficacy, selectivity and favorable pharmacological properties and lead compounds extensively characterized in terms of biological targets and effects. SELDI-TOF and affinity chromatography on immobilized inhibitors (partners 10 and 11) will be two essential approaches, respectively to rationalize drug development and to understand their cellular mode of action in both parasite and host cells. Favourable ADME and drug-like properties and GMP-compatible synthesis protocols will be taken into account as early as possible in the selection of hits and optimization of leads to enhance our chances for rapid development of drugs usable in anti- leishmanial treatments.