Thomas Michael Frimurer

Thomas Michael Frimurer

Associate Professor

Member of:

    ORCID: 0000-0002-9682-8245

    Introductory remarks on publicationslist

    Publications: Author or co-author on > 40 papers in peer-reviewed, medium to high profile scientific journals. Involved in innovation and commercialization activities. Patents: Author or co-author on > 15 patents on chemical leads and drug candidates for the treatment of obesity, type-2 diabetes, asthma inflammation and pain. Most recently (Mar. 2014) we patented a strong chemical package on oral available small molecule GPR39 agonists – a potential obesity and type-2 diabetes target. Invited talks: Participated in multiple oral presentations at international and national scientific meetings.

     


    Publication year:
    All
    1 - 50 out of 73Page size: 50
    Sort by: Title
    1. Published

      6-Acylamino-2-amino-4-methylquinolines as potent melanin-concentrating hormone 1 receptor antagonists

      Ulven, Trond, Little, P. B., Receveur, J., Frimurer, Thomas Michael, Rist, Ø., Nørregaard, P. K., Mathiesen, Jesper M. & Högberg, T., 2006, In: Bioorganic & Medicinal Chemistry Letters. 16, 4, p. 1070-1075 6 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    2. Published

      6-Acylamino-2-aminoquinolines as Potent Melanin-Concentrating Hormone 1 Receptor Antagonists

      Ulven, Trond, Frimurer, Thomas Michael, Receveur, J., Little, P. B., Rist, Ø., Nørregaard, P. K. & Högberg, T., 2005, In: Journal of Medicinal Chemistry. 48, 18, p. 5684-5697 14 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    3. Published

      A physicogenetic method to assign ligand-binding relationships between 7TM receptors

      Frimurer, Thomas Michael, Ulven, Trond, Elling, T. C. E., Gerlach, L. O., Kostenis, E. & Högberg, T., 2005, In: Bioorganic & Medicinal Chemistry Letters. 15, 16, p. 3707-3712 6 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    4. Published

      A pseudo-sequence method for comparing 7TM receptors with respect to the physicochemical properties of their binding sites

      Frimurer, Thomas Michael, Ulven, Trond, Högberg, T. & Elling, C. E., 2004, Patent No. WO 2004/079625

      Research output: Patent

    5. Published

      Allosteric and orthosteric sites in CC chemokine receptor (CCR5), a chimeric receptor approach

      Thiele, S., Steen, A., Jensen, P. C., Mokrosinski, J., Frimurer, Thomas Michael & Rosenkilde, Mette, 2011, In: Journal of Biological Chemistry. 286, 43, p. 37543-54 12 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    6. Published

      Allostery in Coagulation Factor VIIa Revealed by Ensemble Refinement of Crystallographic Structures

      Sørensen, A. B., Madsen, J. J., Frimurer, Thomas Michael, Overgaard, M. T., Gandhi, P. S., Persson, E. & Olsen, O. H., 2019, In: Biophysical Journal. 116, 10, p. 1823-1835

      Research output: Contribution to journal › Journal article › Research › peer-review

    7. Published

      An aromatic region to induce a switch between agonism and inverse agonism at the ghrelin receptor

      Els, S., Schild, E., Petersen, P. S., Kilian, T., Mokrosinski, J., Frimurer, Thomas Michael, Chollet, C., Schwartz, Thue W., Holst, Birgitte & Beck-Sickinger, A. G., 13 Sep 2012, In: Journal of Medicinal Chemistry. 55, 17, p. 7437-49 13 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    8. Published

      Assessment and Challenges of Ligand Docking into Comparative Models of G-Protein Coupled Receptors

      Nguyen, E. D., Meiler, J., Norn, C. & Frimurer, Thomas Michael, 2 Jul 2013, In: PLOS ONE. 8, 7, p. e67302 19 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    9. Published

      Biased Gs Versus Gq Proteins and β-Arrestin Signaling in the NK1 Receptor Determined by Interactions in the Water Hydrogen Bond Network

      Valentin-Hansen, L., Frimurer, Thomas Michael, Mokrosinski, J., Holliday, N. D. & Schwartz, Thue W., 2 Oct 2015, In: The Journal of Biological Chemistry. 290, 40, p. 24495-508 14 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    10. Published

      Biased Signaling of CCL21 and CCL19 Does Not Rely on N-Terminal Differences, but Markedly on the Chemokine Core Domains and Extracellular Loop 2 of CCR7

      Jørgensen, Astrid Sissel, Larsen, Olav, Uetz-von Allmen, E., Lückmann, Michael, Legler, D. F., Frimurer, Thomas Michael, Veldkamp, C. T., Hjortø, Gertrud Malene & Rosenkilde, Mette, 2019, In: Frontiers in Immunology. 10, 14 p., 2156.

      Research output: Contribution to journal › Journal article › Research › peer-review

    11. Published

      Biased agonism and allosteric modulation of GPR183- a 7TM receptor also known as EBV-induced EBI2

      Daugvilaite, V., Madsen, C. M., Lückmann, Michael, Castello Echeverria, C., Sailer, A. W., Frimurer, Thomas Michael, Rosenkilde, Mette & Benned-Jensen, T., 2017, In: British Journal of Pharmacology. 174, 13, p. 2031–2042

      Research output: Contribution to journal › Journal article › Research › peer-review

    12. Published

      Biased and Constitutive Signaling in the CC-Chemokine Receptor CCR5 by manipulating the Interface between Transmembrane Helix 6 and 7

      Steen, A., Thiele, S., Guo, D., Gasbjerg, Lærke Smidt, Frimurer, Thomas Michael & Rosenkilde, Mette, 3 May 2013, In: Journal of Biological Chemistry. 288, 18, p. 12511-12521 11 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    13. Published

      Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast

      Bradley, S. A., Lehka, B. J., Hansson, F. G., Adhikari, K. B., Rago, D., Rubaszka, P., Haidar, A. K., Chen, L., Hansen, L. G., Gudich, O., Giannakou, K., Lengger, B., Gill, R. T., Nakamura, Y., de Bernonville, T. D., Koudounas, K., Romero-Suarez, D., Ding, L., Qiao, Y., Frimurer, T. M. & 12 others, Petersen, A. A., Besseau, S., Kumar, S., Gautron, N., Melin, C., Marc, J., Jeanneau, R., O’Connor, S. E., Courdavault, V., Keasling, J. D., Zhang, J. & Jensen, M. K., 2023, In: Nature Chemical Biology. 19, 12, p. 1551-1560 10 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    14. Published

      CRTH2 receptor ligands for therapeutic use

      Ulven, Trond, Frimurer, Thomas Michael, Rist, Ø., Kostenis, E., Högberg, T., Receveur, J. & Grimstrup, M., 2005, Patent No. WO 2005/115382 A1

      Research output: Patent

    15. Published

      CRTH2 receptor ligands for therapeutic use - B-series

      Ulven, Trond, Frimurer, Thomas Michael, Rist, Ø., Kostenis, E. & Högberg, T., 2005, Patent No. WO 2005/115374 A1

      Research output: Patent

    16. Published

      Cyclic Quinoline compounds for use in MCH receptor related disorders

      Frimurer, Thomas Michael, Ulven, Trond, Högberg, T., Nørregaard, P. K., Little, P. B. & Receveur, J., 2004, Patent No. WO 2004/052371

      Research output: Patent

    17. Published

      Deciphering specificity and cross-reactivity in tachykinin NK1 and NK2 receptors

      Madsen, J. J., Petersen, Jacob Emil, Christensen, D. P., Hansen, J. B., Schwartz, Thue W., Frimurer, Thomas Michael & Olsen, O. H., 2023, In: Journal of Biological Chemistry. 299, 12, 11 p., 105438.

      Research output: Contribution to journal › Journal article › Research › peer-review

    18. Published

      Discovery of GPR183 Agonists Based on an Antagonist Scaffold

      Kjær, Viktoria Madeline Skovgaard, Ieremias, L., Daugvilaite, V., Lückmann, Michael, Frimurer, Thomas Michael, Ulven, Trond, Rosenkilde, Mette & Våbenø, J., 2021, In: ChemMedChem. 16, 17, p. 2623-2627

      Research output: Contribution to journal › Journal article › Research › peer-review

    19. Published

      Downregulation of 5-HT7 Serotonin Receptors by the Atypical Antipsychotics Clozapine and Olanzapine. Role of Motifs in the C-Terminal Domain and Interaction with GASP-1

      Manfra, O., Van Craenenbroeck, K., Skieterska, K., Frimurer, Thomas Michael, Schwartz, Thue W., Levy, F. O. & Andressen, K. W., Jul 2015, In: A C S Chemical Neuroscience. 6, 7, p. 1206–1218 13 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    20. Published

      Exploration of SAR features by modifications of thiazoleacetic acids as CRTH2 antagonists

      Grimstrup, M., Receveur, J. M., Rist, Ø., Frimurer, Thomas Michael, Nielsen, P. A., Mathiesen, Jesper M. & Högberg, T., 1 Mar 2010, In: Bioorganic and Medicinal Chemistry Letters. 20, 5, p. 1638-1641 4 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    21. Published

      Extracellular succinate hyperpolarizes M2 macrophages through SUCNR1/GPR91-mediated Gq signaling

      Trauelsen, Mette, Hiron, T. K., Lin, D., Petersen, Jacob Emil, Breton, B., Husted, Anna Sofie, Hjorth, Siv Annegrethe, Inoue, A., Frimurer, Thomas Michael, Bouvier, M., O'Callaghan, C. A. & Schwartz, Thue W., 2021, In: Cell Reports. 35, 11, 15 p., 109246.

      Research output: Contribution to journal › Journal article › Research › peer-review

    22. Published

      GLP-1 Val8: A Biased GLP-1R Agonist with Altered Binding Kinetics and Impaired Release of Pancreatic Hormones in Rats

      van der Velden, W. J. C., Smit, F. X., Christiansen, Charlotte Bayer, Møller, T. C., Hjortø, Gertrud Malene, Larsen, Olav, Schiellerup, S. P., Bräuner, Hans, Holst, Jens Juul, Hartmann, Bolette, Frimurer, Thomas Michael & Rosenkilde, Mette, 2021, In: ACS Pharmacology & Translational Science. 4, 1, p. 296-313 18 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    23. Published

      GPR40 (FFAR1) – Combined Gs and Gq signaling in vitro is associated with robust incretin secretagogue action ex vivo and in vivo

      Pedersen, M. H., Bentsen, M. A., Husted, Anna Sofie, Ekberg, J. P., Wright, M. J., Di Salvo, J., Weinglass, A. B., Engelstoft, M. S., Madsen, A. N., Lückmann, Michael, Miller, M. W., Trujillo, M. E., Frimurer, Thomas Michael, Holst, Birgitte, Howard, A. D. & Schwartz, Thue W., Jan 2015, In: Molecular Metabolism. 4, 1, p. 3-14 12 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    24. Published

      Gating function of isoleucine-116 in TM-3 (position III:16/3.40) for the activity state of the CC-chemokine receptor 5 (CCR5)

      Steen, A., wbf943, wbf943, Thiele, S., Guo, D., Frimurer, Thomas Michael & Rosenkilde, Mette, Mar 2014, In: British Journal of Pharmacology. 171, 6, p. 1566-79 14 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    25. Published

      H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids

      Nakamura, K., Saredi, G., Becker, J. R., Foster, B. M., Nguyen, N. V., Beyer, T. E., Cesa, L. C., Faull, P. A., Lukauskas, S., Frimurer, Thomas Michael, Chapman, J. R., Bartke, T. & Groth, Anja, 2019, In: Nature Cell Biology. 21, 3, p. 311-318

      Research output: Contribution to journal › Letter › Research › peer-review

    26. Published

      Human substance P receptor binding mode of the antagonist drug aprepitant by NMR and crystallography

      Chen, S., Lu, M., Liu, D., Yang, L., Yi, C., Ma, L., Zhang, H., Liu, Q., Frimurer, Thomas Michael, Wang, M., Schwartz, Thue W., Stevens, R. C., Wu, B., Wuthrich, K. & Zhao, Q., 2019, In: Nature Communications. 10, 8 p., 638.

      Research output: Contribution to journal › Journal article › Research › peer-review

    27. Published

      In Silico Investigation of the Neurotensin Receptor 1 Binding Site: Overlapping Binding Modes for Small Molecule Antagonists and the Endogenous Peptide Agonist

      Lückmann, Michael, Holst, Birgitte, Schwartz, Thue W. & Frimurer, Thomas Michael, 2016, In: Molecular Informatics. 35, p. 19-24 6 p.

      Research output: Contribution to journal › Letter › Research › peer-review

    28. Published

      Inhibiting RHOA Signaling in Mice Increases Glucose Tolerance and Numbers of Enteroendocrine and Other Secretory Cells in the Intestine

      Petersen, N., Frimurer, Thomas Michael, Pedersen, M. T., Egerod, Kristoffer Lihme, Albrechtsen, Nicolai Jacob Wewer, Holst, Jens Juul, Grapin-Botton, A., Jensen, Kim Bak & Schwartz, Thue W., 2018, In: Gastroenterology. 155, 4, p. 1164-1176 4 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    29. Published

      Investigating GIPR (ant)agonism: A structural analysis of GIP and its receptor

      Smit, F. X., van der Velden, W. J. C., Kizilkaya, Hüsün Sheyma, Nørskov, A., Lückmann, Michael, Hansen, T. N., wbf943, wbf943, Qvotrup, K., Frimurer, Thomas Michael & Rosenkilde, Mette, 2021, In: Structure. 29, 7, p. 679-693.e6 21 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    30. Published

      Ligand-selective small molecule modulators of the constitutively active vGPCR US28

      Amarandi, R., Lückmann, Michael, Melynis, M., Jakobsen, M. H., Fallah, Z., Spiess, Katja, Hjortø, Gertrud Malene, Pui, A., Frimurer, Thomas Michael & Rosenkilde, Mette, 2018, In: European Journal of Medicinal Chemistry. 155, p. 244-254

      Research output: Contribution to journal › Journal article › Research › peer-review

    31. Published

      Mechanistic basis of GPCR activation explored by ensemble refinement of crystallographic structures

      Madsen, J. J., Ye, L., Frimurer, Thomas Michael & Olsen, O. H., 2022, In: Protein Science. 31, 11, 16 p., e4456.

      Research output: Contribution to journal › Journal article › Research › peer-review

    32. Published

      Melanin concentrating hormone receptor 1 (MCHR1) antagonists - Still a viable approach for obesity treatment?

      Högberg, T., Frimurer, Thomas Michael & Sasmal, P. K., 1 Oct 2012, In: Bioorganic & Medicinal Chemistry Letters. 22, 19, p. 6039-6047 9 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    33. Published

      Model-Based Discovery of Synthetic Agonists for the Zn2+-Sensing G-Protein-Coupled Receptor 39 (GPR39) Reveals Novel Biological Functions.

      Frimurer, Thomas Michael, Mende, F., Graae, A., Engelstoft, M. S., Egerod, Kristoffer Lihme, Nygaard, R., Gerlach, L., Hansen, J. B., Schwartz, Thue W. & Holst, Birgitte, 2017, In: Journal of Medicinal Chemistry. 60, 3, p. 886-898 13 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    34. Published

      Modulation in selectivity and allosteric properties of small-molecule ligands for CC-chemokine receptors

      Thiele, S., Malmgaard-Clausen, M., Engel-Andreasen, J., Steen, A., Rummel, P. C., Nielsen, M. C., Gloriam, David E., Frimurer, Thomas Michael, Ulven, Trond & Rosenkilde, Mette, 27 Sep 2012, In: Journal of Medicinal Chemistry. 55, 18, p. 8164-77 14 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    35. Published

      Modulation of constitutive activity and signaling bias of the ghrelin receptor by conformational constraint in the second extracellular loop

      Mokrosinski, J., Frimurer, Thomas Michael, Sivertsen, B., Schwartz, Thue W. & Holst, Birgitte, Sep 2012, In: Journal of Biological Chemistry. 287, p. 33488-33502 15 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    36. Published

      Molecular Mechanism of Action for Allosteric Modulators and Agonists in CC-chemokine Receptor 5 (CCR5)

      Karlshøj, S., Amarandi, R. M., Larsen, Olav, Daugvilaite, V., Steen, A., Brvar, M., Pui, A., Frimurer, Thomas Michael, Ulven, Trond & Rosenkilde, Mette, 23 Dec 2016, In: Journal of Biological Chemistry. 291, 52, p. 26860-26874

      Research output: Contribution to journal › Journal article › Research › peer-review

    37. Published

      Molecular characterization of oxysterol binding to the Epstein-Barr virus-induced gene 2 (GPR183)

      Benned-Jensen, T., Norn, C., Laurent, S., Madsen, C. M., Larsen, H. M., Arfelt, K. N., Wolf, R. M., Frimurer, Thomas Michael, Sailer, A. W. & Rosenkilde, Mette, 12 Oct 2012, In: The Journal of Biological Chemistry. 287, 42, p. 35470-83 14 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    38. Published

      Molecular dynamics-based identification of binding pathways and two distinct high-affinity sites for succinate in succinate receptor 1/GPR91

      Iliyaz, Aslihan Shenol, Lückmann, Michael, Trauelsen, Mette, Lambrughi, M., Tiberti, M., Papaleo, E., Frimurer, Thomas Michael & Schwartz, Thue W., 2024, In: Molecular Cell. 84, 5, p. 955-966.e4 17 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    39. Published

      Molecular dynamics-guided discovery of an ago-allosteric modulator for GPR40/FFAR1

      Lückmann, Michael, Trauelsen, Mette, Bentsen, M. A., Nissen, T. A. D., Martins, J., Fallah, Z., Nygaard, M. M., Papaleo, E., Lindorff-Larsen, Kresten, Schwartz, Thue W. & Frimurer, Thomas Michael, 2 Apr 2019, In: Proceedings of the National Academy of Sciences of the United States of America. 116, 14, p. 7123-7128

      Research output: Contribution to journal › Journal article › Research › peer-review

    40. Published

      Molecular mechanism of ligand binding pathways and activation of the succinate receptor

      Iliyaz, Aslihan Shenol, Lückmann, Michael, Trauelsen, Mette, Frimurer, Thomas Michael & Schwartz, Thue W., 2021, In: European Biophysics Journal. 50, Suppl. 1, p. 160 1 p., P-234.

      Research output: Contribution to journal › Conference abstract in journal › Research

    41. Published

      Mutation-Guided Unbiased Modeling of the Fat Sensor GPR119 for High-Yield Agonist Screening.

      Norn, C., Pedersen, M. H., Engelstoft, M. S., Kim, S. H., Lehmann, J., Jones, R. M., Schwartz, Thue W. & Frimurer, Thomas Michael, 2015, In: Structure. 23, 12, p. 2377-2386 10 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    42. Published

      Novel selective orally active CRTH2 antagonists for allergic inflammation developed from in silico derived hits

      Ulven, Trond, Receveur, J., Grimstrup, M., Rist, Ø., Frimurer, Thomas Michael, Gerlach, L., Mathiesen, Jesper M., Kostenis, E., Uller, L. & Högberg, T., 2006, In: Journal of Medicinal Chemistry. 49, 23, p. 6638-6641 4 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    43. Published

      Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 1

      Rist, O., Grimstrup, M., Receveur, J., Frimurer, Thomas Michael, Ulven, Trond, Kostenis, E. & Högberg, T., 4 Dec 2009, In: Bioorganic & Medicinal Chemistry Letters. 20, 3, p. 1177-1180 4 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    44. Published

      Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 2

      Grimstrup, M., Rist, Ø., Receveur, J., Frimurer, Thomas Michael, Ulven, Trond, Mathiesen, Jesper M., Kostenis, E. & Högberg, T., 1 Feb 2010, In: Bioorganic & Medicinal Chemistry Letters. 20, 3, p. 1181-1185 5 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    45. Published

      Optimisation of in silico derived 2-aminobenzimidazole hits as unprecedented selective kappa opioid receptor agonists

      Sasmal, P. K., Krishna, C. V., Sudheerkumar Adabala, S., Rawoof, K. A., Thadi, A., Sukumar, K. P., Cheera, S., Abbineni, C., Rao, K. V. L. N., Prasanthi, A., Nijhawan, K., Jaleel, M., Ramachandran Iyer, L., Chaitanya, T. K., Tiwari, N. K., Krishna, N. L., Potluri, V., Khanna, I., Frimurer, T. M., Lückmann, M. & 3 others, Rist, Ø., Elster, L. & Högberg, T., 15 Feb 2015, In: Bioorganic & Medicinal Chemistry Letters. 25, 4, p. 887-92 6 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    46. Published

      Optimization of First-in-Class Dual-Acting FFAR1/FFAR4 Allosteric Modulators with Novel Mode of Action

      Lückmann, Michael, Iliyaz, Aslihan Shenol, Nissen, T. A. D., Petersen, Jacob Emil, Kouvchinov, David, Schwartz, Thue W. & Frimurer, Thomas Michael, 2022, In: ACS Medicinal Chemistry Letters. 13, 12, p. 1839-1847

      Research output: Contribution to journal › Journal article › Research › peer-review

    47. Published

      PheVI:09 (Phe6.44) as a sliding microswitch in seven-transmembrane (7TM) G protein-coupled receptor activation

      Valentin-Hansen, L., Holst, Birgitte, Frimurer, Thomas Michael, Schwartz, Thue W. & Hansen, L. V., 21 Dec 2012, In: Journal of Biological Chemistry. 287, 52, p. 43516-43526 11 p.

      Research output: Contribution to journal › Journal article › Research › peer-review

    48. Published

      Phenoxyacetic acid derivatives as CRTH2 receptor ligands, their preparation, pharmaceutical compositions, and use in therapy

      Ulven, Trond, Frimurer, Thomas Michael, Rist, Ø., Kostenis, E., Högberg, T., Receveur, J. & Grimstrup, M., 2007, Patent No. WO 2007/062678 A1

      Research output: Patent

    49. Published

      Preassociation between the 5-HT7 serotonin receptor and G protein Gs: molecular determinants and association with low potency activation of adenylyl cyclase

      Ulsund, A. H., Dahl, M., Frimurer, Thomas Michael, Manfra, O., Schwartz, Thue W., Levy, F. O. & Andressen, K. W., 2019, In: FASEB Journal. 33, 3, p. 3870-3886

      Research output: Contribution to journal › Journal article › Research › peer-review

    50. Published

      Preparation of phenyl benzoyl pyrazoles as CRTH2 receptor ligands

      Ulven, Trond, Frimurer, Thomas Michael, Rist, O., Kostenis, E., Hoegberg, T., Receveur, J. & Grimstrup, M., 2005, Patent No. WO 2005/115382 A1

      Research output: Patent

    Previous 1 2 Next

    ID: 34520257