Publications

Solinas, G., Breasson, L., Becattini, B., Sardi, C., Molinaro, A., Marone, R., Botindari, F., Bousquenaud, M., Ruegg, C. and Wymann, M. (2017) ‘The role of PI3K gamma signaling within leukocytes in obesity-driven inflammation and insulin resistance’, EUROPEAN JOURNAL OF CLINICAL INVESTIGATION. WILEY.   
Breasson, L., Becattini, B., Sardi, C., Molinaro, A., Zani, F., Marone, R., Botindari, F., Bousquenaud, M., Ruegg, C., Wymann, M. P. and Solinas, G. (2017) ‘PI3K gamma activity in leukocytes promotes adipose tissue inflammation and early-onset insulin resistance during obesity’, SCIENCE SIGNALING. AMER ASSOC ADVANCEMENT SCIENCE, 10(488). doi: 10.1126/scisignal.aaf2969.   
Breasson, L., Becattini, B., Sardi, C., Molinaro, A., Zani, F., Marone, R., Botindari, F., Bousquenaud, M., Ruegg, C., Wymann, M. P. and Solinas, G. (2017) ‘PI3Kgamma activity in leukocytes promotes adipose tissue inflammation and early-onset insulin resistance during obesity’, Science signaling, 10(488). doi: 10.1126/scisignal.aaf2969.   
Beaufils, F., Cmiljanovic, N., Cmiljanovic, V., Bohnacker, T., Melone, A., Marone, R., Jackson, E., Zhang, X., Sele, A., Borsari, C., Mestan, J., Hebeisen, P., Hillmann, P., Giese, B., Zvelebil, M., Fabbro, D., Williams, R. L., Rageot, D. and Wymann, M. P. (2017) ‘5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology’, JOURNAL OF MEDICINAL CHEMISTRY. AMER CHEMICAL SOC, 60(17), pp. 7524-7538. doi: 10.1021/acs.jmedchem.7b00930.   
Bohnacker, T., Prota, A. E., Beaufils, F., Burke, J. E., Melone, A., Inglis, A. J., Rageot, D., Sele, A. M., Cmiljanovic, V., Cmiljanovic, N., Bargsten, K., Aher, A., Akhmanova, A., Fernando Diaz, J., Fabbro, D., Zvelebil, M., Williams, R. L., Steinmetz, M. O. and Wymann, M. P. (2017) ‘Deconvolution of Buparlisib’s mechanism of action defines specific PI3K and tubulin inhibitors for therapeutic intervention’, NATURE COMMUNICATIONS. NATURE PUBLISHING GROUP, 8. doi: 10.1038/ncomms14683.   
Beaufils, F., Cmiljanovic, N., Cmiljanovic, V., Bohnacker, T., Melone, A., Marone, R., Jackson, E., Zhang, X., Sele, A., Borsari, C., Mestan, J., Hebeisen, P., Hillmann, P., Giese, B., Zvelebil, M., Fabbro, D., Williams, R. L., Rageot, D. and Wymann, M. P. (2017) ‘5‑(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology’, Figshare. doi: 10.1021/acs.jmedchem.7b00930.s001.   
Beaufils, F., Rageot, D., Melone, A., Lang, M., Mestan, J., Cmiljanovic, V., Hillmann, P., Hebeisen, P., Fabbro, D. and Wymann, M. P. (2016) ‘Structure-activity relationship studies, synthesis, and biological evaluation of PQR620, a highly potent and selective mTORC1/2 inhibitor’, CANCER RESEARCH. AMER ASSOC CANCER RESEARCH. doi: 10.1158/1538-7445.AM2016-1336.   
Sele, A. M., Rageot, D., Bohnacker, T., Beaufils, F., Prota, A. E., Steinmetz, M. O. and Wymann, M. P. (2016) ‘Novel 4-(pyrimidin-2-yl)morpholines targeting the colchicine-binding site of tubulin’, CANCER RESEARCH. AMER ASSOC CANCER RESEARCH. doi: 10.1158/1538-7445.AM2016-1364.   
Lupieri, A., Smirnova, N. F., Malet, N. F., Arnal, J. F., Martinez, L. O., Wymann, M., Hirsch, E., Gayral, S. and Laffargue, M. (2016) ‘Absence of PI3Kg leads to increased reendothelialization in mice through modulation of IP-10 secretion’, CARDIOVASCULAR RESEARCH. OXFORD UNIV PRESS. doi: 10.1093/cvr/cvw137.   
Beaufils, F., Rageot, D., Melone, A., Sele, A., Lang, M., Mestan, J., Ettlin, R. A., Hillmann, P., Cmiljanovic, V., Walter, C., Singer, E., Nguyen, H. H. P., Hebeisen, P., Fabbro, D. and Wymann, M. P. (2016) ‘Pharmacological characterization of the selective, orally bioavailable, potent mTORC1/2 inhibitor PQR620’, CANCER RESEARCH. AMER ASSOC CANCER RESEARCH. doi: 10.1158/1538-7445.AM2016-393A.   
Botindari, F. and Wymann, M. (2015) ‘Dual targeting of PI3K gamma and SHIP1 for a synergistic inhibition of IgE mediated mast cell activation’, FEBS JOURNAL. WILEY-BLACKWELL.   
Tarantelli, C., Gaudio, E., Kwee, I., Rinaldi, A., Bernasconi, E., Cascione, L., Hillmann, P., Stathis, A., Carrassa, L., Broggini, M., Stussi, G., Fabbro, D., Beaufils, F., Melone, A., Bohnacker, T., Wymann, M. P., Wicki, A., Zucca, E., Cmiljanovic, V. and Bertoni, F. (2015) ‘Pre-clinical activity and mechanism of action of the novel dual PI3K/mTOR inhibitor PQR309 in B-cell lymphomas’, CANCER RESEARCH. AMER ASSOC CANCER RESEARCH. doi: 10.1158/1538-7445.AM2015-2652.   
Cmiljanovic, V., Cmiljanovic, N., Marone, R., Beaufils, F., Zhang, X., Zvelebil, M., Hebeisen, P., Lang, M., Mestan, J., Melone, A., Bohnacker, T., Gaudio, E., Tarantelli, C., Bertoni, F., Ritschard, R., Pretre, V., Wicki, A., Fabbro, D., Hillmann, P., Williams, R., Giese, B. and Wymann, M. P. (2015) ‘PQR309: Structure-based design, synthesis and biological evaluation of a novel, selective, dual pan-PI3K/mTOR inhibitor’, CANCER RESEARCH. AMER ASSOC CANCER RESEARCH. doi: 10.1158/1538-7445.AM2015-2664.   
Cmiljanovic, V., Ettlin, R. A., Beautils, F., Dieterle, W., Hillmann, P., Mestan, J., Melone, A., Bohnacker, T., Lang, M., Cmiljanovic, N., Giese, B., Hebeisen, P., Wymann, M. P. and Fabbro, D. (2015) ‘PQR309: A potent, brain-penetrant, dual pan-PI3K/mTOR inhibitor with excellent oral bioavailability and tolerability’, CANCER RESEARCH. AMER ASSOC CANCER RESEARCH. doi: 10.1158/1538-7445.AM2015-4514.   
Ettlin, R., Dieterle, W., Fabbro, D., Hebeisen, P., Beaufils, F., Hillmann, P., Stumm, M., Dimitrijevic, S., Wymann, M., Cmiljanovic, N., Giese, B. and Cmiljanovic, V. (2015) ‘Early preclinical development of PQR309, a novel balanced dual PI3K/mTOR inhibitor for treatment of various cancer types’, TOXICOLOGY LETTERS. ELSEVIER IRELAND LTD. doi: 10.1016/j.toxlet.2015.08.963.   
Bohnacker, T., Beaufils, F., Prota, A. E., Burke, J. E., Melone, A., Inglis, A. J., Fusco, L., Cmiljanovic, V., Cmiljanovic, N., Rageot, D., Bargsten, K., Saez-Calvo, G., Pertz, O., Aher, A. B., Akhmanova, A., Diaz, F. J., Fabbro, D., Zvelebil, M., Williams, R. L., Steinmetz, M. O. and Wymann, M. P. (2015) ‘BKM120-mediated G2 arrest: Structural and functional segregation of off-target action and PI3K inhibition’, CANCER RESEARCH. AMER ASSOC CANCER RESEARCH. doi: 10.1158/1538-7445.AM2015-671.   
Zimmermann, M., Cal, R., Janett, E., Hoffmann, V., Bochet, C. G., Constable, E., Beaufils, F. and Wymann, M. P. (2014) ‘Cell-Permeant and Photocleavable Chemical Inducer of Dimerization’, Angewandte Chemie International Edition. Wiley, 53(18), pp. 4717-4720. doi: 10.1002/anie.201310969.   edoc
Smirnova, N. F., Gayral, S., Pedros, C., Loirand, G., Vaillant, N., Malet, N., Kassem, S., Calise, D., Goudouneche, D., Wymann, M. P., Hirsch, E., Gadeau, A. P., Martinez, L. O., Saoudi, A. and Laffargue, M. (2014) ‘Targeting PI3Kgamma activity decreases vascular trauma-induced intimal hyperplasia through modulation of the Th1 response’, J Exp Med, 211(9), pp. 1779-1792. doi: 10.1084/jem.20131276.   
Gayral, S., Garnotel, R., Castaing-Berthou, A., Blaise, S., Fougerat, A., Berge, E., Montheil, A., Malet, N., Wymann, M. P., Maurice, P., Debelle, L., Martiny, L., Martinez, L. O., Pshezhetsky, A. V., Duca, L. and Laffargue, M. (2014) ‘Elastin-derived peptides potentiate atherosclerosis through the immune Neu1-PI3Kγ pathway’, Cardiovascular research, 102(1), pp. 118-127. doi: 10.1093/cvr/cvt336.   
Wymann, M. P. and Solinas, G. (2013) ‘Inhibition of phosphoinositide 3-kinase γ attenuates inflammation, obesity, and cardiovascular risk factors’, Annals of the New York Academy of Sciences. Blackwell Publishing, Vol. 1280, pp. 44-47. doi: 10.1111/nyas.12037.   edoc
Zotes, T. M., Arias, C. F., Fuster, J. J., Spada, R., Perez-Yague, S., Hirsch, E., Wymann, M., Carrera, A. C., Andres, V. and Barber, D. F. (2013) ‘PI3K p110γ deletion attenuates murine atherosclerosis by reducing macrophage proliferation but not polarization or apoptosis in lesions’, PLoS ONE. Public Library of Science, Vol. 8, H. 8 , e72674. doi: 10.1371/journal.pone.0072674.   edoc
Barthwal, M. K., Anzinger, J. J., Xu, Q., Bohnacker, T., Wymann, M. P. and Kruth, H. S. (2013) ‘Fluid-phase pinocytosis of native low density lipoprotein promotes murine M-CSF differentiated macrophage foam cell formation’, PLoS ONE. Public Library of Science, 8(3), p. e58054. doi: 10.1371/journal.pone.0058054.   edoc
Wymann, M. P. and Simons, K. (2013) ‘Membrane dynamics in physiology and disease’, The FEBS journal. Blackwell, 280(12), p. 2729. doi: 10.1111/febs.12322.   edoc
Walser, R., Burke, J. E., Gogvadze, E., Bohnacker, T., Zhang, X., Hess, D., Kuenzi, P., Leitges, M., Hirsch, E., Williams, R. L., Laffargue, M. and Wymann, M. P. (2013) ‘PKCβ phosphorylates PI3Kγ to activate it and release it from GPCR control’, PLoS Biology. Public Library of Science, 11(6), p. e1001587. doi: 10.1371/journal.pbio.1001587.   edoc
Schmidt, C., Schneble, N., Muller, J. P., Bauer, R., Perino, A., Marone, R., Rybalkin, S. D., Wymann, M. P., Hirsch, E. and Wetzker, R. (2013) ‘Phosphoinositide 3-kinase gamma mediates microglial phagocytosis via lipid kinase-independent control of cAMP’, Neuroscience. Elsevier, Vol. 233, pp. 44-53. doi: 10.1016/j.neuroscience.2012.12.036.   edoc
Collmann, E., Bohnacker, T., Marone, R., Dawson, J., Rehberg, M., Stringer, R., Krombach, F., Burkhart, C., Hirsch, E., Hollingworth, G. J., Thomas, M. and Wymann, M. P. (2013) ‘Transient targeting of phosphoinositide 3-kinase acts as a roadblock in mast cells’ route to allergy’, Journal of allergy and clinical immunology. Mosby, 132(4), pp. 959-968. doi: 10.1016/j.jaci.2013.03.008.   edoc
Erhart, D., Zimmermann, M., Jacques, O., Wittwer, M. B., Ernst, B., Constable, E., Zvelebil, M., Beaufils, F. and Wymann, M. P. (2013) ‘Chemical development of intracellular protein heterodimerizers’, Chemistry & Biology. Cell Press, 20(4), pp. 549-557. doi: 10.1016/j.chembiol.2013.03.010.   edoc
Wymann, M. P. and Schultz, C. (2012) ‘The chemical biology of phosphoinositide 3-kinases’, ChemBioChem. Wiley-VCH, 13(14), pp. 2022-2035. doi: 10.1002/cbic.201200089.   edoc
Fougerat, A., Smirnova, N. F., Gayral, S., Malet, N., Hirsch, E., Wymann, M. P., Perret, B., Martinez, L. O., Douillon, M. and Laffargue, M. (2012) ‘Key role of PI3Kgamma in monocyte chemotactic protein-1-mediated amplification of PDGF-induced aortic smooth muscle cell migration’, British journal of pharmacology. Nature Publishing Group, 166(5), pp. 1643-1653. doi: 10.1111/j.1476-5381.2012.01866.x.   edoc
Reichel, C. A., Puhr-Westerheide, D., Zuchtriegel, G., Uhl, B., Berberich, N., Zahler, S., Wymann, M. P., Luckow, B. and Krombach, F. (2012) ‘C-C motif chemokine CCL3 and canonical neutrophil attractants promote neutrophil extravasation through common and distinct mechanisms’, Blood. American Society of Hematology, 120(4), pp. 880-890. doi: 10.1182/blood-2012-01-402164.   edoc
Harris, S. J., Ciuclan, L., Finan, P. M., Wymann, M. P., Walker, C., Westwick, J., Ward, S. G. and Thomas, M. J. (2012) ‘Genetic ablation of PI3Kgamma results in defective IL-17RA signalling in T lymphocytes and increased IL-17 levels’, European journal of immunology. Verl. Chemie, 42(12), pp. 3394-3404. doi: 10.1002/eji.201242463.   edoc
Schaefer, T., Zajonz, A., Lorentz, P., Bohnacker, T., Wymann, M. P. and Schweighoffer, T. (2012) ‘Luminal decoration of blood vessels by activated perivasal mast cells in allergic rhinitis’, Allergy. Munksgaard, 67(4), pp. 510-520. doi: 10.1111/j.1398-9995.2012.02790.x.   edoc
Anzinger, J. J., Chang, J., Xu, Q., Barthwal, M. K., Bohnacker, T., Wymann, M. P. and Kruth, H. S. (2012) ‘Murine bone marrow-derived macrophages differentiated with GM-CSF become foam cells by PI3K?-dependent fluid-phase pinocytosis of native LDL’, Journal of Lipid Research. American Society for Biochemistry and Molecular Biology, 53(1), pp. 34-42. doi: 10.1194/jlr.M018887.   edoc | Open Access
Wymann, M. (2012) ‘PI3Ks-drug targets in inflammation and cancer’, Subcellular biochemistry. Springer, Vol. 58, pp. 111-181. doi: 10.1007/978-94-007-3012-0_5.   edoc
Reichel, C. A., Lerchenberger, M., Uhl, B., Rehberg, M., Berberich, N., Zahler, S., Wymann, M. P. and Krombach, F. (2011) ‘Plasmin inhibitors prevent leukocyte accumulation and remodeling events in the postischemic microvasculature’, PLoS ONE. Public Library of Science, 6(2), p. e17229. doi: 10.1371/journal.pone.0017229.   edoc
Becattini, B., Marone, R., Zani, F., Arsenijevic, D., Seydoux, J., Montani, J.-P., Dulloo, A. G., Thorens, B., Preitner, F., Wymann, M. P. and Solinas, G. (2011) ‘PI3Kγ within a nonhematopoietic cell type negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance’, Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 108(42), pp. E854-63. doi: 10.1073/pnas.1106698108.   edoc
Perino, A., Ghigo, A., Ferrero, E., Morello, F., Santulli, G., Baillie, G. S., Damilano, F., Dunlop, A. J., Pawson, C., Walser, R., Levi, R., Altruda, F., Silengo, L., Langeberg, L. K., Neubauer, G., Heymans, S., Lembo, G., Wymann, M. P., Wetzker, R., Houslay, M. D., Iaccarino, G., Scott, J. D. and Hirsch, E. (2011) ‘Integrating cardiac PIP3 and cAMP signaling through a PKA anchoring function of p110γ’, Molecular cell. Cell Press, 42(1), pp. 84-95. doi: 10.1016/j.molcel.2011.01.030.   edoc
Wymann, M. P. and Wenk, M. R. (2011) ‘Neutral not a loss : phosphoinositides beyond the head group’, Nature methods. Nature Publishing Group, 8(3), pp. 219-220. doi: 10.1038/nmeth0311-219.   edoc
Spitzenberg, V., König, C., Ulm, S., Marone, R., Röpke, L., Müller, J. P., Grün, M., Bauer, R., Rubio, I., Wymann, M. P., Voigt, A. and Wetzker, R. (2010) ‘Targeting PI3K in neuroblastoma’, Journal of cancer research and clinical oncology. Springer, 136(12), pp. 1881-1890. doi: 10.1007/s00432-010-0847-2.   edoc
Ciraolo, E., Morello, F., Hobbs, R. M., Wolf, F., Marone, R., Iezzi, M., Lu, X., Mengozzi, G., Altruda, F., Sorba, G., Guan, K., Pandolfi, P. P., Wymann, M. P. and Hirsch, E. (2010) ‘Essential role of the p110beta subunit of phosphoinositide 3-OH kinase in male fertility’, Molecular Biology of the Cell. American Society for Cell Biology, 21(5), pp. 704-711. doi: 10.1091/mbc.E09-08-0744.   edoc | Open Access
Thomas, M., Edwards, M. J., Sawicka, E., Duggan, N., Hirsch, E., Wymann, M. P., Owen, C., Trifilieff, A., Walker, C., Westwick, J. and Finan, P. (2009) ‘Essential role of phosphoinositide 3-kinase gamma in eosinophil chemotaxis within acute pulmonary inflammation’, Immunology : an official journal of the British Society for Immunology. Blackwell, 126(3), pp. 413-422.   edoc
Bohnacker, T., Marone, R., Collmann, E., Calvez, R., Hirsch, E. and Wymann, M. P. (2009) ‘PI3Kgamma adaptor subunits define coupling to degranulation and cell motility by distinct PtdIns(3,4,5)P3 pools in mast cells’, Science signaling : the signal transduction knowledge environment. American Association for the Advancement of Science, 2(74), p. ra27.   edoc
Santos-Sierra, S., Deshmukh, S. D., Kalnitski, J., Küenzi, P., Wymann, M. P., Golenbock, D. T. and Henneke, P. (2009) ‘Mal connects TLR2 to PI3Kinase activation and phagocyte polarization’, The EMBO journal. Nature Publishing Group, 28(14), pp. 2018-2027.   edoc
Kurig, B., Shymanets, A., Bohnacker, T., Prajwal, Brock, C., Ahmadian, M. R., Schaefer, M., Gohla, A., Harteneck, C., Wymann, M. P., Jeanclos, E. and Nürnberg, B. (2009) ‘Ras is an indispensable coregulator of the class IB phosphoinositide 3-kinase p87/p110gamma’, Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 106(48), pp. 20312-20317.   edoc
Barberis, L., Pasquali, C., Bertschy-Meier, D., Cuccurullo, A., Costa, C., Ambrogio, C., Vilbois, F., Chiarle, R., Wymann, M., Altruda, F., Rommel, C. and Hirsch, E. (2009) ‘Leukocyte transmigration is modulated by chemokine-mediated PI3Kgamma-dependent phosphorylation of vimentin’, European journal of immunology. Verl. Chemie, 39(4), pp. 1136-1146.   edoc
Marone, R., Erhart, D., Mertz, A. C., Bohnacker, T., Schnell, C., Cmiljanovic, V., Stauffer, F., Garcia-Echeverria, C., Giese, B., Maira, S.-M. and Wymann, M. P. (2009) ‘Targeting melanoma with dual phosphoinosite 3-kinase/mammalian target of rapamycin inhibitors’, Molecular Cancer Research. AACR, 7(4), pp. 601-613.   edoc
Wymann, M. P. and Schneiter, R. (2008) ‘Lipid signalling in disease’, Nature reviews. Molecular cell biology. Nature Publishing Group, 9(2), pp. 162-176.   edoc
Ciraolo, E., Iezzi, M., Marone, R., Marengo, S., Curcio, C., Costa, C., Azzolino, O., Gonella, C., Rubinetto, C., Wu, H., Dastrù, W., Martin, E. L., Silengo, L., Altruda, F., Turco, E., Lanzetti, L., Musiani, P., Rückle, T., Rommel, C., Backer, J. M., Forni, G., Wymann, M. P. and Hirsch, E. (2008) ‘Phosphoinositide 3-kinase p110beta activity : key role in metabolism and mammary gland cancer but not development’, Science signaling. American Association for the Advancement of Science, 1(36), p. ra3.   edoc
Marone, R., Cmiljanovic, V., Giese, B. and Wymann, M. P. (2008) ‘Targeting phosphoinositide 3-kinase-Moving towards therapy’, Biochimica et biophysica acta. Elsevier, 1784(1), pp. 159-185.   edoc
Fougerat, A., Gayral, S., Gourdy, P., Schambourg, A., Rückle, T., Schwarz, M. K., Rommel, C., Hirsch, E., Arnal, J. F., Salles, J. P., Perret, B., Breton-Douillon, M., Wymann, M. P. and Laffargue, M. (2008) ‘Genetic and pharmacological targeting of phosphoinositide 3-kinase-gamma reduces atherosclerosis and favors plaque stability by modulating inflammatory processes’, Circulation. Lippincott Williams & Wilkins, 117(10), pp. 1310-1317.   edoc
Hui, R. C., Gomes, A. R., Constantinidou, D., Costa, J. R., Karadedou, C. T., Fernandez de Mattos, S., Wymann, M. P., Brosens, J. J., Schulze, A. and Lam, E. W. (2008) ‘The forkhead transcription factor FOXO3a increases phosphoinositide-3 kinase/Akt activity in drug-resistant leukemic cells through induction of PIK3CA expression’, MOL CELL BIOL, 28, pp. 5886-5898.