Discovery of a novel inhibitor against urokinase-type plasminogen activator, a potential enzyme with a role in atherosclerotic plaque instability

References

• Artimo, P., Jonnalagedda, M., Arnold, K., Baratin, D., Csardi, G., de Castro, E., Duvaud, S., Flegel, V., Fortier, A., Gasteiger, E., Grosdidier, A., Hernandez, C., Ioannidis, V., Kuznetsov, D., Liechti, R., Moretti, S., Mostaguir, K., Redaschi, N., Rossier, G., Xenarios, I., & Stockinger, H. (2012). ExPASy: SIB bioinformatics resource portal. Nucleic Acids Research, 40(Web Server issue), W597–W603.
   PubMedGoogle Scholar
• Baricos, W. H., Cortez, S. L., El-Dahr, S. S., & Schnaper, H. W. (1995). ECM degradation by cultured human mesangial cells is mediated by a PA/plasmin/MMP-2 cascade. Kidney International, 47(4), 1039–1047. https://doi.org/10.1038/ki.1995.150
   PubMed Web of Science ®Google Scholar
• Basatemur, G. L., Jørgensen, H. F., Clarke, M. C., Bennett, M. R., & Mallat, Z. (2019). Vascular smooth muscle cells in atherosclerosis. Nature Reviews. Cardiology, 16(12), 727–744.
   PubMed Web of Science ®Google Scholar
• Bauer, A. (2013). Investigation of the regulatory role of heme oxygenase-1 and its products during VEGF-induced angiogenesis, using in vitro and in vivo models. (Doctoral dissertation). Imperial College London.
   Google Scholar
• Bennett, M. R. (1999). Apoptosis of vascular smooth muscle cells in vascular remodelling and atherosclerotic plaque rupture. Cardiovascular Research, 41(2), 361–368. https://doi.org/10.1016/S0008-6363(98)00212-0
   PubMed Web of Science ®Google Scholar
• Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., … Bourne, P. E. (2000). The protein data bank. Nucleic Acids Research, 28(1), 235–242. https://doi.org/10.1093/nar/28.1.235
   PubMed Web of Science ®Google Scholar
• Blasi, F., & Carmeliet, P. (2002). uPAR: A versatile signalling orchestrator. Nature Reviews. Molecular Cell Biology, 3(12), 932–943.
   PubMed Web of Science ®Google Scholar
• Capriotti, E., Fariselli, P., & Casadio, R. (2005). I-Mutant2. 0: predicting stability changes upon mutation from the protein sequence or structure. Nucleic acids research, 33, 306-310.
   Google Scholar
• Cho, K. Y., Miyoshi, H., Kuroda, S., Yasuda, H., Kamiyama, K., Nakagawara, J., Takigami, M., Kondo, T., & Atsumi, T. (2013). The phenotype of infiltrating macrophages influences arteriosclerotic plaque vulnerability in the carotid artery. Journal of Stroke and Cerebrovascular Diseases: The Official Journal of National Stroke Association, 22(7), 910–918.
   PubMed Web of Science ®Google Scholar
• Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1), 42717–42713. https://doi.org/10.1038/srep42717
   PubMed Web of Science ®Google Scholar
• Davies, M. J. (2000). The pathophysiology of acute coronary syndromes. Heart (British Cardiac Society), 83(3), 361–366. https://doi.org/10.1136/heart.83.3.361
   PubMed Web of Science ®Google Scholar
• Degryse, B. (2011). Editorial [Hot topic: The urokinase receptor system as strategic therapeutic target: Challenges for the 21st century (Executive Guest Editor: Bernard Degryse). Current Pharmaceutical Design, 17(19), 1872–1873. https://doi.org/10.2174/138161211796718161
   PubMed Web of Science ®Google Scholar
• DeLano, W. L. (2002). Pymol: An open-source molecular graphics tool. CCP4 Newsletter on Protein Crystallography, 40(1), 82–92.
   Google Scholar
• Fan, H., Schneidman-Duhovny, D., Irwin, J. J., Dong, G., Shoichet, B. K., & Sali, A. (2011). Statistical potential for modeling and ranking of protein–ligand interactions. Journal of Chemical Information and Modeling, 51(12), 3078–3092.
   PubMed Web of Science ®Google Scholar
• Fitridge, R., & Thompson, M. (2011). Mechanisms of vascular disease: A reference book for vascular specialists (p. 587). University of Adelaide Press.
   Google Scholar
• Frostegård, J. (2013). Immunity, atherosclerosis and cardiovascular disease. BMC Medicine, 11(1), 117–113. https://doi.org/10.1186/1741-7015-11-117
   PubMed Web of Science ®Google Scholar
• Fuhrman, B. (2012). The urokinase system in the pathogenesis of atherosclerosis. Atherosclerosis, 222(1), 8–14. https://doi.org/10.1016/j.atherosclerosis.2011.10.044
   PubMed Web of Science ®Google Scholar
• Garcia-Touchard, A., Henry, T. D., Sangiorgi, G., Spagnoli, L. G., Mauriello, A., Conover, C., & Schwartz, R. S. (2005). Extracellular proteases in atherosclerosis and restenosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 25(6), 1119–1127.
   PubMed Web of Science ®Google Scholar
• Glaser, F., Pupko, T., Paz, I., Bell, R. E., Bechor-Shental, D., Martz, E., & Ben-Tal, N. (2003). ConSurf: Identification of functional regions in proteins by surface-mapping of phylogenetic information. Bioinformatics (Oxford, England), 19(1), 163–164. https://doi.org/10.1093/bioinformatics/19.1.163
   PubMed Web of Science ®Google Scholar
• Hess, B., Kutzner, C., Van Der Spoel, D., & Lindahl, E. (2008). GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation. Journal of Chemical Theory and Computation, 4(3), 435–447.
   PubMed Web of Science ®Google Scholar
• Jones, G., Willett, P., Glen, R. C., Leach, A. R., & Taylor, R. (1997). Development and validation of a genetic algorithm for flexible docking. Journal of Molecular Biology, 267(3), 727–748.
   PubMed Web of Science ®Google Scholar
• Kadar, A., & Glasz, T. (2001). Development of atherosclerosis and plaque biology. Cardiovascular Surgery, 9(2), 109–121.
   PubMedGoogle Scholar
• Kang, L., Li, H., Jiang, H., & Wang, X. (2009). An improved adaptive genetic algorithm for protein–ligand docking. Journal of Computer-Aided Molecular Design, 23(1), 1–12.
   PubMed Web of Science ®Google Scholar
• Khosravi, M., Hosseini-Fard, R., & Najafi, M. (2018). Circulating low density lipoprotein (LDL). Hormone Molecular Biology and Clinical Investigation, 35(2), 1-12. https://doi.org/10.1515/hmbci-2018-0024
   Google Scholar
• Kimble-Hill, A. C. (2008). Biophysical mechanisms of protein recruitment to raft domains studied using planar model membranes [Doctoral dissertation]. Purdue University.
   Google Scholar
• Kruth, H. S. (2001). Macrophage foam cells and atherosclerosis. Frontiers in Bioscience: A Journal and Virtual Library, 6(1), D429–D455. https://doi.org/10.2741/kruth
   PubMedGoogle Scholar
• Kufareva, I., Ilatovskiy, A. V., & Abagyan, R. (2012). Pocketome: An encyclopedia of small-molecule binding sites in 4D. Nucleic Acids Research, 40(Database issue), D535–D540.
   PubMedGoogle Scholar
• Kumari, R., Kumar, R., & Lynn, A. (2014). g_mmpbsa-a GROMACS tool for high-throughput MM-PBSA calculations. Journal of Chemical Information and Modeling, 54(7), 1951–1962. https://doi.org/10.1021/ci500020m
   PubMed Web of Science ®Google Scholar
• Kunamneni, A., Ravuri, B. D., Saisha, V., Ellaiah, P., & Prabhakhar, T. (2008). Urokinase-a very popular cardiovascular agent. Recent Patents on Cardiovascular Drug Discovery, 3(1), 45–58. https://doi.org/10.2174/157489008783331670
   PubMedGoogle Scholar
• Lacolley, P., Regnault, V., Segers, P., & Laurent, S. (2017). Vascular smooth muscle cells and arterial stiffening: Relevance in development, aging, and disease. Physiological Reviews, 97(4), 1555–1617.
   PubMed Web of Science ®Google Scholar
• Laskowski, R. A., & Swindells, M. B. (2011). LigPlot+: Multiple ligand–protein interaction diagrams for drug discovery, 51(10), 2778-2786.
   Google Scholar
• Lijnen, H. R. (2002). Extracellular proteolysis in the development and progression of atherosclerosis. Biochemical Society Transactions, 30(2), 163–167. https://doi.org/10.1042/bst0300163
   PubMedGoogle Scholar
• Lipinski, C. A. (2004). Lead- and drug-like compounds: The rule-of-five revolution. Drug Discovery Today. Technologies, 1(4), 337–341. https://doi.org/10.1016/j.ddtec.2004.11.007
   PubMedGoogle Scholar
• Lu, P., Takai, K., Weaver, V. M., & Werb, Z. (2011). Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harbor Perspectives in Biology, 3(12), a005058. https://doi.org/10.1101/cshperspect.a005058
   PubMed Web of Science ®Google Scholar
• Mahmood, N., Mihalcioiu, C., & Rabbani, S. A. (2018). Multifaceted role of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR): Diagnostic, prognostic, and therapeutic applications. Frontiers in Oncology, 8, 24. https://doi.org/10.3389/fonc.2018.00024
   PubMed Web of Science ®Google Scholar
• Maple, H. J., Clayden, N., Baron, A., Stacey, C., & Felix, R. (2019). Developing degraders: principles and perspectives on design and chemical space. MedChemComm, 10(10), 1755–1764.
   PubMed Web of Science ®Google Scholar
• Mitu, O., Cirneala, I. A., Lupsan, A. I., Iurciuc, M., Mitu, I., Dimitriu, D. C., Costache, A. D., Petris, A. O., & Costache, I. I. (2020). The effect of vitamin supplementation on subclinical atherosclerosis in patients without manifest cardiovascular diseases: Never-ending hope or underestimated effect? Molecules, 25(7), 1717. https://doi.org/10.3390/molecules25071717
   PubMed Web of Science ®Google Scholar
• Mondino, A., & Blasi, F. (2004). uPA and uPAR in fibrinolysis, immunity and pathology. Trends in Immunology, 25(8), 450–455.
   PubMed Web of Science ®Google Scholar
• Moriwaki, H., Stempien-Otero, A., Kremen, M., Cozen, A. E., & Dichek, D. A. (2004). Overexpression of urokinase by macrophages or deficiency of plasminogen activator inhibitor type 1 causes cardiac fibrosis in mice. Circulation Research, 95(6), 637–644. https://doi.org/10.1161/01.RES.0000141427.61023.f4
   PubMed Web of Science ®Google Scholar
• Mysinger, M. M., Carchia, M., Irwin, J. J., & Shoichet, B. K. (2012). Directory of useful decoys, enhanced (DUD-E): Better ligands and decoys for better benchmarking. Journal of Medicinal Chemistry, 55(14), 6582–6594.
   PubMed Web of Science ®Google Scholar
• Ossowski, L., & Aguirre-Ghiso, J. A. (2000). Urokinase receptor and integrin partnership: coordination of signaling for cell adhesion, migration and growth. Current Opinion in Cell Biology, 12(5), 613–620.
   PubMed Web of Science ®Google Scholar
• Paland, N., Aharoni, S., & Fuhrman, B. (2013). Urokinase-type plasminogen activator (uPA) modulates monocyte-to-macrophage differentiation and prevents Ox-LDL-induced macrophage apoptosis. Atherosclerosis, 231(1), 29–38.
   PubMed Web of Science ®Google Scholar
• Paland, N., & Fuhrman, B. (2014). The Importance of the Urokinase-Type Plasminogen Activator and Its Receptor for the Development and Progression of Atherosclerosis. In Role of Proteases in Cellular Dysfunction(pp. 263–277). New York, NY: Springer.
   Google Scholar
• Parra, R. G., Schafer, N. P., Radusky, L. G., Tsai, M. Y., Guzovsky, A. B., Wolynes, P. G., & Ferreiro, D. U. (2016). Protein Frustratometer 2: A tool to localize energetic frustration in protein molecules, now with electrostatics. Nucleic Acids Research, 44(W1), W356–W360.
   PubMed Web of Science ®Google Scholar
• Pawlak, K., Buraczewska-Buczko, A., Pawlak, D., & Mysliwiec, M. (2010). Hyperfibrinolysis, uPA/suPAR system, kynurenines, and the prevalence of cardiovascular disease in patients with chronic renal failure on conservative treatment. The American Journal of the Medical Sciences, 339(1), 5–9. https://doi.org/10.1097/MAJ.0b013e3181b922a4
   PubMed Web of Science ®Google Scholar
• Sander, T., Freyss, J., von Korff, M., & Rufener, C. (2015). DataWarrior: An open-source program for chemistry aware data visualization and analysis. Journal of Chemical Information and Modeling, 55(2), 460–473.
   PubMed Web of Science ®Google Scholar
• Santos, G. B., Ganesan, A., & Emery, F. S. (2016). Oral administration of peptide-based drugs: beyond Lipinski's rule. ChemMedChem, 11(20), 2245–2251.
   PubMed Web of Science ®Google Scholar
• Schmitt, M., Wilhelm, O., Jänicke, F., Magdolen, V., Reuning, U., Ohi, H., Moniwa, N., Kobayashi, H., Weidle, U., & Graeff, H. (1995). Urokinase‐type plasminogen activator (uPA) and its receptor (CD87): A new target in tumor invasion and metastasis. Journal of Obstetrics and Gynaecology, 21(2), 151–165. https://doi.org/10.1111/j.1447-0756.1995.tb01089.x
   Google Scholar
• Schüttelkopf, A. W., & Van Aalten, D. M. (2004). PRODRG: A tool for high-throughput crystallography of protein–ligand complexes. Acta Crystallographica Section D Biological Crystallography, 60(8), 1355–1363. https://doi.org/10.1107/S0907444904011679
   PubMedGoogle Scholar
• Shah, P. K. (2003). Mechanisms of plaque vulnerability and rupture. Journal of the American College of Cardiology, 41(4), S15–S22. https://doi.org/10.1016/S0735-1097(02)02834-6
   PubMed Web of Science ®Google Scholar
• Skjøt-Arkil, H., Barascuk, N., Register, T., & Karsdal, M. A. (2010). Macrophage-mediated proteolytic remodeling of the extracellular matrix in atherosclerosis results in neoepitopes: A potential new class of biochemical markers. Assay and Drug Development Technologies, 8(5), 542–552.
   PubMed Web of Science ®Google Scholar
• Steins, M. B., Padró, T., Schwaenen, C., Ruiz, S., Mesters, R. M., Berdel, W. E., & Kienast, J. (2004). Overexpression of urokinase receptor and cell surface urokinase-type plasminogen activator in the human vessel wall with different types of atherosclerotic lesions. Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis, 15(5), 383–391. https://doi.org/10.1097/01.mbc.0000114441.59147.56
   PubMed Web of Science ®Google Scholar
• Sterling, T., & Irwin, J. J. (2015). ZINC 15–ligand discovery for everyone. Journal of Chemical Information and Modeling, 55(11), 2324–2337.
   PubMed Web of Science ®Google Scholar
• Tan, E. M., Uitto, J., Collagens, A., Fibronectin, D., Elastin, B., & Proteoglycans, D. (1989). Pathology of the extracellular matrix in atherosclerosis: In vivo and in vitro models. Atherosclerosis and Arteriosclerosis, 87, 12-13.
   Google Scholar
• Tian, W., Chen, C., Lei, X., Zhao, J., & Liang, J. (2018). CASTp 3.0: Computed atlas of surface topography of proteins. Nucleic Acids Research, 46(W1), W363–W367.
   PubMed Web of Science ®Google Scholar
• Tkachuk, V., Stepanova, V., Little, P. J., & Bobik, A. (1996). Regulation and role of urokinase plasminogen activator in vascular remodelling. Clinical and Experimental Pharmacology & Physiology, 23(9), 759–765.
   PubMed Web of Science ®Google Scholar
• Tuttolomondo, A., Di Raimondo, D., Pecoraro, R., Arnao, V., Pinto, A., & Licata, G. (2012). Atherosclerosis as an inflammatory disease. Current Pharmaceutical Design, 18(28), 4266–4288. https://doi.org/10.2174/138161212802481237
   PubMed Web of Science ®Google Scholar
• Van Aalten, D. M., Bywater, R., Findlay, J. B., Hendlich, M., Hooft, R. W., & Vriend, G. (1996). PRODRG, a program for generating molecular topologies and unique molecular descriptors from coordinates of small molecules. Journal of Computer-Aided Molecular Design, 10(3), 255–262.
   PubMed Web of Science ®Google Scholar
• Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A. E., & Berendsen, H. J. (2005). GROMACS: Fast, flexible, and free. Journal of Computational Chemistry, 26(16), 1701–1718.
   PubMed Web of Science ®Google Scholar
• Verdonk, M. L., Cole, J. C., Hartshorn, M. J., Murray, C. W., & Taylor, R. D. (2003). Improved protein–ligand docking using GOLD. Proteins: Structure, Function, and Bioinformatics, 52(4), 609–623. https://doi.org/10.1002/prot.10465
   PubMed Web of Science ®Google Scholar
• Xu, S., Bendeck, M., & Gotlieb, A. I. (2016). Vascular pathobiology: Atherosclerosis and large vessel disease. In L. Maximilian Buja and Jagdish Butany (Eds.), Cardiovascular pathology (pp. 85–124). Academic Press.  https://doi.org/10.1016/B978-0-12-420219-1.00003-3
   Google Scholar