Networks and drug design

Description:

Despite improved rational drug design and a remarkable progress in genomic, proteomic and high-throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade. The project is aimed to find novel drug targets, which are less vulnerable to the development of resistance, and to the mobilization of secondary pathways of cellular networks. As a part of this effort, design strategies to find appropriate target-sets of multi-target drugs are to be developed using multiple perturbations of protein-protein interaction networks.

Publications:

1. Modos, D., Brooks, J., Fazekas, D., Ari, E., Vellai, T., Csermely, P., Korcsmáros, T. and Lenti, K. (2016) Identification of critical paralog groups with indispensable roles in the regulation of signaling flow. Sci. Rep. 6, 38588, IF: 5.2 Download it!
2. Csermely, P., Korcsmaros, T. and Nussinov, R. (2016) Intracellular and intercellular signaling networks in cancer initiation, development and precision anti-cancer therapy. RAS acts as contextual signaling hub. Sem. Cell Dev. Biol. 58, 55-59, IF: 6.3 Download it!
3. Adami, H.-O., Csermely, P., Veres, D.V., Emilsson, L., Loberg, M., Bretthauer, M. and Kalager, M. 2016. Are rapidly growing cancers more lethal? Eur. J. Cancer. in press, IF: 6.2 Download it!
4. Korcsmaros, T., Modos, D., Bulusu, K., Fazekas, D., Kubisch, J., Brooks, J., Marczell, I., Szabo, P., Vellai, T., Csermely, P., Lenti, K. and Bender, A. (2016) Neighbours of cancer-related proteins have key influence on pathogenesis and could increase the drug target space for anti-cancer therapies. Systems Biology and Applications, in press.
5. Perez-Lopez, A. R., Szalay, K.Z., Türei, D., Módos, D., Lenti, K., Korcsmáros, T. and Csermely, P. (2015) Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations. Sci. Rep. 5, 10182. IF: 5.0 Download it!
6. Csermely, P., Hódsági, J., Korcsmáros, T., Módos, D., Perez-Lopez, A.R., Szalay, K., Veres, D.V., Lenti, K., Wu, L.Y. and Zhang, X.S. (2015) Cancer stem cells display extremely large evolvability: alternating plastic and rigid networks as a potential mechanism. Network models, novel therapeutic target strategies and the contributions of hypoxia, inflammation and cellular senescence. Seminars in Cancer Biology, 30, 42-51. IF: 9.1 .http://arxiv.org/abs/1312.6356
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7. Szalay, K.Z., Nussinov, R. and Csermely, P. (2014) Attractor structures of signaling networks: Consequences of different conformational barcode dynamics and their relations to network-based drug design. Molecular Informatics, 33: 463-468. IF: 2.3 http://arxiv.org/abs/1404.4515 Download it!
8. Csermely, P. and Korcsmáros, T. (2013) Cancer-related networks: a help to understand, predict and change malignant transformation Seminars in Cancer Biology 23, 252-261, Download it!
9. Gyurko, D.M., Veres, D.V., Modos, D., Lenti, K., Korcsmaros, T. and Csermely, P. (2013) Adaptation and learning of molecular networks as a description of cancer development at the systems-level: Potential use in anti-cancer therapies. Seminars in Cancer Biology 23, 262-269, http://arxiv.org/abs/1306.3371. IF: 6.5
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10. Szilágyi, A., Nussinov, R. and Csermely P. (2013) Allo-network drugs: extension of the allosteric drug concept to protein-protein interaction and signaling networks. Curr. Top. Med. Chem. in press, IF: 4.2 Download it!
11. Csermely, P., Korcsmáros, T., Kiss, H.J.M., London, G. and Nussinov, R. (2013) Structure and dynamics of biological networks: a novel paradigm of drug discovery. A comprehensive review. Pharmacol. Therap. 138, 333-408, IF: 8.6, http://arxiv.org/abs/1210.0330
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    • Received 2 times 3-star recommendations by Faculty of 1000 (F1000 Prime)
12. Nussinov, R., Tsai, C.-J. and Csermely, P. (2011) Allo-network drugs: harnessing allostery in cellular networks. Trends in Pharmacol. Sci. 32, 686-693, IF: 11.0 -- a cover story. Download it!
13. Farkas, I.J., Korcsmáros, T., Kovács, I.A., Mihalik, Á., Palotai, R., Simkó, G.I., Szalay, K.Z., Szalay-Bekő, M., Vellai, T., Wang, S. and Csermely, P. (2011) Network-based tools in the identification of novel drug-targets. Science Signaling 4, pt3. Download the paper!
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14. Spiró, Z., Kovács I.A. and Csermely, P. (2008) Insights from networks of drugs, therapies, targets and diseases and the prediction of novel drug targets. J. Biol. 7, 20.
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15. Antal, M.A., Böde, C. and Csermely, P. (2009) Perturbation waves in proteins and protein networks: Applications of percolation and game theories in signaling and drug design. Curr. Pept. Prot. Res. 10, 161-172  Download it!
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16. Agoston, V., Csermely, P. and Pongor, S. (2005) Multiple, weak hits confuse complex systems. Phys. Rev. E. 71, 051909,
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17. Csermely, P., Ágoston, V. and Pongor, S. (2005) The efficiency of multi-target drugs: the network approach might help drug design. Trends Pharmacol. Sci. 26, 178-182
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18. Korcsmáros, T., Szalay, M., Böde. C., Kovács, I.A., and Csermely, P. (2007) How to design multi-target drugs: Target-search options in cellular networks. Exp. Op. Drug Discovery 2: 1-10. Download it!