JBM  Vol.5 No.3 , March 2017
Construction of Enriched Resource for Primary Therapeutic Targets of Approved and Clinical Trial Drugs
An assessment of the efficacy targets of drugs that represent an opportunity for targeted therapy is fundamental to the development of post-genomic research strategies within the pharmaceutical industry. Identification and validation of efficacy target is an important process in drug discovery and development. Extensive drug discovery efforts have yielded many approved and candidate drugs. Although sever drug databases provide the drug and their corresponding targets, there is an insufficient coverage of the clinical trial drugs over the past decades. Here, we conduct a comprehensive survey for current clinical trial drugs, therapeutic targets. The analysis contents include: 1) collect clinical trial drugs from different sources, 2) By analysis of the literature, we summarize the criteria for assign therapeutic targets for each drug based on its indication. The knowledge of these drugs and their targets is useful not only for drug discovery and development of targeted therapy, but also for facilitating the discovery of systems pharmacology.
Cite this paper: Yang, H. , Yu, C. , Li, Y. and Zhu, F. (2017) Construction of Enriched Resource for Primary Therapeutic Targets of Approved and Clinical Trial Drugs. Journal of Biosciences and Medicines, 5, 1-6. doi: 10.4236/jbm.2017.53001.

[1]   Hopkins, A.L. and Groom, C.R. (2002) The Druggable Genome. Nature Reviews. Drug Discovery, 1, 727-730.

[2]   Imming, P., Sinning, C. and Meyer, A. (2006) Drugs, Their Targets and the Nature and Number of Drug Targets. Nature Reviews. Drug Discovery, 5, 821-834.

[3]   Zheng, C.J., Han, L.Y., Yap, C.W., Ji, Z.L., Cao, Z.W. and Chen, Y.Z. (2006) Therapeutic Targets: Progress of Their Exploration and Investigation of Their Characteristics. Pharmacological Reviews, 58, 259-279.

[4]   Engelman, J.A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J.O., Lindeman, N., Gale, C.M., Zhao, X., Christensen, J., et al. (2007) MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling. Science, 316, 1039-1043.

[5]   Chen, Z., Cheng, K., Walton, Z., Wang, Y., Ebi, H., Shimamura, T., Liu, Y., Tupper, T., Ouyang, J., Li, J., et al. (2012) A Murine Lung Cancer Co-Clinical Trial Identifies Genetic Modifiers of Therapeutic Response. Nature, 483, 613-617.

[6]   Barabasi, A.L., Gulbahce, N. and Loscalzo, J. (2011) Network Medicine: A Net-work-Based Approach to Human Disease. Nature Reviews. Genetics, 12, 56-68.

[7]   Zhao, S. and Iyengar, R. (2012) Systems Pharmacology: Network Analysis to Identify Multiscale Mechanisms of Drug Action. Annual Review of Pharmacology and Toxicology, 52, 505-521.

[8]   Csermely, P., Agoston, V. and Pongor, S. (2005) The Efficiency of Multi-Target Drugs: The Network Approach Might Help Drug Design. Trends in Pharmacological Sciences, 26, 178-182.

[9]   Jia, J., Zhu, F., Ma, X., Cao, Z., Li, Y. and Chen, Y.Z. (2009) Mechanisms of Drug Combinations: Interaction and Network Perspectives. Nature Reviews. Drug Discovery, 8, 111-128.

[10]   Law, V., Knox, C., Djoumbou, Y., Jewison, T., Guo, A.C., Liu, Y., Maciejewski, A., Arndt, D., Wilson, M., Neveu, V., et al. (2014) DrugBank 4.0: Shedding New Light on Drug Metabolism. Nucleic Acids Research, 42, D1091-1097.

[11]   Qin, C., Zhang, C., Zhu, F., Xu, F., Chen, S.Y., Zhang, P., Li, Y.H., Yang, S.Y., Wei, Y.Q., Tao, L., et al. (2014) Therapeutic Target Database Update 2014: A Resource for Targeted Therapeutics. Nucleic Acids Research, 42, D1118-1123.

[12]   Pawson, A.J., Sharman, J.L., Benson, H.E., Faccenda, E., Alexander, S.P., Buneman, O.P., Davenport, A.P., McGrath, J.C., Peters, J.A., Southan, C., et al. (2014) The IUPHAR/BPS Guide to PHARMACOLOGY: An Expert-Driven Knowledgebase of Drug Targets and Their Ligands. Nucleic Acids Research, 42, D1098-1106.

[13]   Bento, A.P., Gaulton, A., Hersey, A., Bellis, L.J., Chambers, J., Davies, M., Kruger, F.A., Light, Y., Mak, L., McGlinchey, S., et al. (2014) The ChEMBL Bioactivity Database: An Update. Nucleic Acids Research, 42, D1083-1090.

[14]   Liu, T., Lin, Y., Wen, X., Jorissen, R.N. and Gilson, M.K. (2007) BindingDB: A Web-Accessible Database of Experimentally Determined Protein-Ligand Binding Affinities. Nucleic Acids Research, 35, D198-201.

[15]   Kanehisa, M., Goto, S., Sato, Y., Kawashima, M., Furumichi, M. and Tanabe, M. (2014) Data, Information, Knowledge and Principle: Back to Metabolism in KEGG. Nucleic Acids Research, 42, D199-205.

[16]   Smietana, K., Siatkowski, M. and Moller, M. (2016) Trends in Clinical Success Rates. Nature Reviews. Drug Discovery, 15, 379-380.

[17]   Yang, H., Qin, C., Li, Y.H., Tao, L., Zhou, J., Yu, C.Y., Xu, F., Chen, Z., Zhu, F. and Chen, Y.Z. (2016) Therapeutic Target Database Update 2016: Enriched Resource for Bench to Clinical Drug Target and Targeted Pathway Information. Nucleic Acids Research, 44, D1069-1074.

[18]   Overington, J.P., Al-Lazikani, B. and Hopkins, A.L. (2006) How Many Drug Targets Are There? Nature Reviews. Drug Discovery, 5, 993-996.

[19]   Verstovsek, S., Kantarjian, H., Mesa, R.A., Pardanani, A.D., Cortes-Franco, J., Thomas, D.A., Estrov, Z., Fridman, J.S., Bradley, E.C., Erickson-Viitanen, S., et al. (2010) Safety and Efficacy of INCB018424, a JAK1 and JAK2 Inhibitor, in Myelofibrosis. The New England Journal of Medicine, 363, 1117-1127.

[20]   Gao, B., Doan, A. and Hybertson, B.M. (2014) The Clinical Potential of Influencing Nrf2 Signaling in Degenerative and Immunological Disorders. Clinical Pharmacology: Advances and Applications, 6, 19-34.

[21]   Paul, S.M., Mytelka, D.S., Dunwiddie, C.T., Persinger, C.C., Munos, B.H., Lindborg, S.R. and Schacht, A.L. (2010) How to Improve R&D Productivity: the Pharmaceutical Industry’s Grand Challenge. Nature Reviews. Drug Discovery, 9, 203-214.

[22]   Pammolli, F., Magazzini, L. and Riccaboni, M. (2011) The Productivity Crisis in Pharmaceutical R&D. Nature Reviews. Drug Discovery, 10, 428-438.

[23]   Lipinski, C.A., Lombardo, F., Dominy, B.W. and Feeney, P.J. (2001) Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings. Advanced Drug Delivery Reviews, 46, 3-26.

[24]   Zhu, F., Han, L., Zheng, C., Xie, B., Tammi, M.T., Yang, S., Wei, Y. and Chen, Y. (2009) What Are Next Generation Innovative Therapeutic Targets? Clues from Genetic, Structural, Physicochemical, and Systems Profiles of Successful Targets. The Journal of Pharmacology and Experimental Therapeutics, 330, 304-315.