Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT

International audienceBackground: The stem cell factor receptor, KIT, is a target for the treatment of cancer, mastocytosis, and inflammatory diseases. Here, we characterise the in vitro and in vivo profiles of masitinib (AB1010), a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT. Methodology/Principal Findings: In vitro, masitinib had greater activity and selectivity against KIT than imatinib, inhibiting recombinant human wild-type KIT with an half inhibitory concentration (IC50) of 200 ± 40 nM and blocking stem cell factor-induced proliferation and KIT tyrosine phosphorylation with an IC50 of 150 ± 80 nM in Ba/F3 cells expressing human or mouse wild-type KIT. Masitinib also potently inhibited recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. In contrast, masitinib demonstrated weak inhibition of ABL and c-Fms and was inactive against a variety of other tyrosine and serine/threonine kinases. This highly selective nature of masitinib suggests that it will exhibit a better safety profile than other tyrosine kinase inhibitors; indeed, masitinib-induced cardiotoxicity or genotoxicity has not been observed in animal studies. Molecular modelling and kinetic analysis suggest a different mode of binding than imatinib, and masitinib more strongly inhibited degranulation, cytokine production, and bone marrow mast cell migration than imatinib. Furthermore, masitinib potently inhibited human and murine KIT with activating mutations in the juxtamembrane domain. In vivo, masitinib blocked tumour growth in mice with subcutaneous grafts of Ba/F3 cells expressing a juxtamembrane KIT mutant. Conclusions: Masitinib is a potent and selective tyrosine kinase inhibitor targeting KIT that is active, orally bioavailable in vivo, and has low toxicit

QAIcar project: Indoor Air Quality in vehicle cabin- odor and microorganism treatment

SSCI-VIDE+CARE+CGU:MHM:PVEInternational audienceSeveral studies have shown that volatile organic compounds (VOCs) can be concentrated in the car, enclosed and confined at rates higher than those of outdoor air [1]. Thus, the air quality is almost always less good inside and is degraded according to external parameters, ex. confined areas of traffic (eg tunnels) [2] or depending on the season (increase in VOC by 40% during summer, due to high temperatures). The presence of these VOCs in vehicle cabin air is responsible for allergies, respiratory problems, skin problems. As people spend a lot of their time in their vehicle [3], for example, in France, 73% of active population (18 million people) use their vehicles every day to go to work and spends an average of 78 minutes per day that is 3 years and 4 months of their life! [4], it is essential to develop an efficient device to remove them. Indeed, most of the actual depollution systems are based on adsorption of these compounds to store them.The QAIcar project aims to develop an air handling equipment dedicated to the automotive interior allowing to destroy microorganisms and VOCs.The project includes 3 innovations:- the coupling of catalysis at room temperature with photocatalysis- the development of a bactericidal luminous textile which will serve support for the coupling of catalyst and photocatalyst.- the concept of a compact reactor integrating the active luminous textile into a multilayer.This project brings together three academic laboratories, IRCELYON, CIRI and LMFA, a small and medium-sized enterprise, Brochier technologies, a mid-size companies, EFI Lighting who is the project leader and two big groups, St; Gobain CREE and the automotive manufacturer, PSA Group.In the poster will be describe the existing locks motivating the project, the objectives, the consortium and the structuring of the project as well as the first results[1] Delaunay C., Goupil G., Ravelomanantsoa H., Person A., Mazoué S., Morawski F., , Pollution atmosphérique 2012 ; 215 : 247 – 258[2] De Pas A., Boissavy-Vineau M., Bull. Epidémiol. Hebd. 2013 ; (1-2) : 17[3] D. Müller, D. Klingelhöfer, S. Uibel, D. A. Groneberg, (2011) J. Occup. Med. Toxicol, 6, 1701-1709[4] Enquête globale transport, STIF, janvier 2013 ; http://www.lievreoutortue.com/dans-votre-vie-combien-de-temps-passerez-vous-dans-votre-voiture

QAIcar project: Indoor Air Quality in vehicle cabin- odor and microorganism treatment

SSCI-VIDE+CARE+CGU:MHM:PVEInternational audienceSeveral studies have shown that volatile organic compounds (VOCs) can be concentrated in the car, enclosed and confined at rates higher than those of outdoor air [1]. Thus, the air quality is almost always less good inside and is degraded according to external parameters, ex. confined areas of traffic (eg tunnels) [2] or depending on the season (increase in VOC by 40% during summer, due to high temperatures). The presence of these VOCs in vehicle cabin air is responsible for allergies, respiratory problems, skin problems. As people spend a lot of their time in their vehicle [3], for example, in France, 73% of active population (18 million people) use their vehicles every day to go to work and spends an average of 78 minutes per day that is 3 years and 4 months of their life! [4], it is essential to develop an efficient device to remove them. Indeed, most of the actual depollution systems are based on adsorption of these compounds to store them.The QAIcar project aims to develop an air handling equipment dedicated to the automotive interior allowing to destroy microorganisms and VOCs.The project includes 3 innovations:- the coupling of catalysis at room temperature with photocatalysis- the development of a bactericidal luminous textile which will serve support for the coupling of catalyst and photocatalyst.- the concept of a compact reactor integrating the active luminous textile into a multilayer.This project brings together three academic laboratories, IRCELYON, CIRI and LMFA, a small and medium-sized enterprise, Brochier technologies, a mid-size companies, EFI Lighting who is the project leader and two big groups, St; Gobain CREE and the automotive manufacturer, PSA Group.In the poster will be describe the existing locks motivating the project, the objectives, the consortium and the structuring of the project as well as the first results[1] Delaunay C., Goupil G., Ravelomanantsoa H., Person A., Mazoué S., Morawski F., , Pollution atmosphérique 2012 ; 215 : 247 – 258[2] De Pas A., Boissavy-Vineau M., Bull. Epidémiol. Hebd. 2013 ; (1-2) : 17[3] D. Müller, D. Klingelhöfer, S. Uibel, D. A. Groneberg, (2011) J. Occup. Med. Toxicol, 6, 1701-1709[4] Enquête globale transport, STIF, janvier 2013 ; http://www.lievreoutortue.com/dans-votre-vie-combien-de-temps-passerez-vous-dans-votre-voiture