دورية أكاديمية
Identifying drug targets in tissues and whole blood with thermal-shift profiling.
العنوان: | Identifying drug targets in tissues and whole blood with thermal-shift profiling. |
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المؤلفون: | Perrin J; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Werner T; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Kurzawa N; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Rutkowska A; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Childs DD; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Kalxdorf M; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Poeckel D; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Stonehouse E; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Strohmer K; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Heller B; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Thomson DW; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Krause J; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Becher I; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Eberl HC; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Vappiani J; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Sevin DC; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Rau CE; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Franken H; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Huber W; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Faelth-Savitski M; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany., Savitski MM; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. mikhail.savitski@embl.de., Bantscheff M; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany. marcus.x.bantscheff@gsk.com., Bergamini G; Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany. giovanna.2.bergamini@gsk.com. |
المصدر: | Nature biotechnology [Nat Biotechnol] 2020 Mar; Vol. 38 (3), pp. 303-308. Date of Electronic Publication: 2020 Jan 20. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Nature America Publishing Country of Publication: United States NLM ID: 9604648 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1696 (Electronic) Linking ISSN: 10870156 NLM ISO Abbreviation: Nat Biotechnol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: New York Ny : Nature America Publishing Original Publication: New York, NY : Nature Pub. Co., [1996- |
مواضيع طبية MeSH: | Blood/*metabolism , Proteome/*chemistry , Proteome/*metabolism , Small Molecule Libraries/*administration & dosage, Animals ; Azepines/administration & dosage ; Azepines/pharmacology ; Hep G2 Cells ; Humans ; Kidney/chemistry ; Kidney/metabolism ; Liver/chemistry ; Liver/metabolism ; Lung/chemistry ; Lung/metabolism ; Male ; Mass Spectrometry ; Mice ; Organ Specificity ; Panobinostat/administration & dosage ; Panobinostat/pharmacology ; Protein Stability ; Rats ; Small Molecule Libraries/pharmacology ; Spleen/chemistry ; Spleen/metabolism ; Testis/chemistry ; Testis/metabolism ; Thermodynamics ; Triazoles/administration & dosage ; Triazoles/pharmacology ; Vemurafenib/administration & dosage ; Vemurafenib/pharmacology |
مستخلص: | Monitoring drug-target interactions with methods such as the cellular thermal-shift assay (CETSA) is well established for simple cell systems but remains challenging in vivo. Here we introduce tissue thermal proteome profiling (tissue-TPP), which measures binding of small-molecule drugs to proteins in tissue samples from drug-treated animals by detecting changes in protein thermal stability using quantitative mass spectrometry. We report organ-specific, proteome-wide thermal stability maps and derive target profiles of the non-covalent histone deacetylase inhibitor panobinostat in rat liver, lung, kidney and spleen and of the B-Raf inhibitor vemurafenib in mouse testis. In addition, we devised blood-CETSA and blood-TPP and applied it to measure target and off-target engagement of panobinostat and the BET family inhibitor JQ1 directly in whole blood. Blood-TPP analysis of panobinostat confirmed its binding to known targets and also revealed thermal stabilization of the zinc-finger transcription factor ZNF512. These methods will help to elucidate the mechanisms of drug action in vivo. |
التعليقات: | Comment in: Trends Pharmacol Sci. 2020 May;41(5):295-297. (PMID: 32192756) |
References: | Bantscheff, M., Lemeer, S., Savitski, M. M. & Kuster, B. Quantitative mass spectrometry in proteomics: critical review update from 2007 to the present. Anal. Bioanal. Chem. 404, 939–965 (2012). (PMID: 10.1007/s00216-012-6203-4) Molina, D. M. et al. Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay. Science 341, 84–87 (2013). (PMID: 10.1126/science.1233606) Savitski, M. M. et al. Tracking cancer drugs in living cells by thermal profiling of the proteome. Science 346, 1255784 (2014). (PMID: 10.1126/science.1255784) Savitski, M. M. et al. Multiplexed proteome dynamics profiling reveals mechanisms controlling protein homeostasis. Cell 173, 260–274 (2018). (PMID: 10.1016/j.cell.2018.02.030) Ishii, T. et al. CETSA quantitatively verifies in vivo target engagement of novel RIPK1 inhibitors in various biospecimens. Sci. Rep. 7, 13000 (2017). (PMID: 10.1038/s41598-017-12513-1) Morgan, P. et al. Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving phase II survival. Drug Discov. Today 17, 419–424 (2012). (PMID: 10.1016/j.drudis.2011.12.020) Bantscheff, M. et al. Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nat. Biotechnol. 29, 255–265 (2011). (PMID: 10.1038/nbt.1759) Becher, I. et al. Thermal profiling reveals phenylalanine hydroxylase as an off-target of panobinostat. Nat. Chem. Biol. 12, 908–910 (2016). (PMID: 10.1038/nchembio.2185) Childs, D Non-parametric analysis of thermal proteome profiles reveals novel drug-binding proteins. Mol. Cell Proteomics 18, 2506–2515 (2019). (PMID: 10.1074/mcp.TIR119.001481) Bhargava, P. & Schnellmann, R. G. Mitochondrial energetics in the kidney. Nat. Rev. Nephrol. 13, 629–646 (2017). (PMID: 10.1038/nrneph.2017.107) van de Poll, M. C. G., Soeters, P. B., Deutz, N. E. P., Fearon, K. C. H. & Dejong, C. H. C. Renal metabolism of amino acids: its role in interorgan amino acid exchange. Am. J. Clin. Nutr. 79, 185–197 (2004). (PMID: 10.1093/ajcn/79.2.185) Reinhard, F. B. M. et al. Thermal proteome profiling monitors ligand interactions with cellular membrane proteins. Nat. Methods 12, 1129–1131 (2015). (PMID: 10.1038/nmeth.3652) Tan, C. S. H. et al. Thermal proximity coaggregation for system-wide profiling of protein complex dynamics in cells. Science 359, 1170–1177 (2018). (PMID: 10.1126/science.aan0346) Gao, B., Wang, H., Lafdil, F. & Feng, D. STAT proteins—key regulators of anti-viral responses, inflammation, and tumorigenesis in the liver. J. Hepatol. 57, 430–441 (2012). (PMID: 10.1016/j.jhep.2012.01.029) Becher, I. et al. Pervasive protein thermal stability variation during the cell cycle. Cell 173, 1495–1507 (2018). (PMID: 10.1016/j.cell.2018.03.053) Mathieson, T. et al. Systematic analysis of protein turnover in primary cells. Nat. Commun. 9, 689 (2018). (PMID: 10.1038/s41467-018-03106-1) Kaneko, T. et al. Assembly pathway of the mammalian proteasome base subcomplex is mediated by multiple specific chaperones. Cell 137, 914–925 (2009). (PMID: 10.1016/j.cell.2009.05.008) Al-Awqati, Q. Plasticity in epithelial polarity of renal intercalated cells: targeting of the H + -ATPase and band 3. Am. J. Physiol. 270, C1571–C1580 (1996). (PMID: 10.1152/ajpcell.1996.270.6.C1571) Kane, P. M. Disassembly and reassembly of the yeast vacuolar H + -ATPase in vivo. J. Biol. Chem. 270, 17025–17032 (1995). (PMID: 7622524) Assessment report Farydak, procedure No. EMA/H/C/003725/0000 (European Medicines Agency, 2015). Bollag, G. et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 467, 596–599 (2010). (PMID: 10.1038/nature09454) Filippakopoulos, P. et al. Selective inhibition of BET bromodomains. Nature 468, 1067–1073 (2010). (PMID: 10.1038/nature09504) Khan, N. et al. Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem. J. 409, 581–589 (2008). (PMID: 10.1042/BJ20070779) Perez-Riverol, Y. et al. The PRIDE database and related tools and resources in 2019: improving support for quantification data. Nucleic Acids Res. 47, D442–D450 (2019). (PMID: 10.1093/nar/gky1106) Franken, H. et al. Thermal proteome profiling for unbiased identification of direct and indirect drug targets using multiplexed quantitative mass spectrometry. Nat. Protoc. 10, 1567–1593 (2015). (PMID: 10.1038/nprot.2015.101) Density and mass of each organ/tissue Bionumbers http://kirschner.med.harvard.edu/files/bionumbers/Density%20and%20mass%20of%20each%20organ-tissue.pdf (2014). Moggridge, S., Sorensen, P. H., Morin, G. B. & Hughes, C. S. Extending the compatibility of the SP3 paramagnetic bead processing approach for proteomics. J. Proteome Res. 17, 1730–1740 (2018). (PMID: 10.1021/acs.jproteome.7b00913) Kelstrup, C. D. et al. Limits for resolving isobaric tandem mass tag reporter ions using phase-constrained spectrum deconvolution. J. Proteome Res. 17, 4008–4016 (2018). (PMID: 10.1021/acs.jproteome.8b00381) Werner, T. et al. Ion coalescence of neutron encoded TMT 10-plex reporter ions. Anal. Chem. 86, 3594–3601 (2014). (PMID: 10.1021/ac500140s) Savitski, M. M. et al. Measuring and managing ratio compression for accurate iTRAQ/TMT quantification. J. Proteome. Res. 12, 3586–3598 (2013). (PMID: 10.1021/pr400098r) Savitski, M. M. et al. Targeted data acquisition for improved reproducibility and robustness of proteomic mass spectrometry assays. J. Am. Soc. Mass. Spectrom. 21, 1668–1679 (2010). (PMID: 10.1016/j.jasms.2010.01.012) Poole, W., Gibbs, D. L., Shmulevich, I., Bernard, B. & Knijnenburg, T. A. Combining dependent P-values with an empirical adaptation of Brown’s method. Bioinformatics 32, i430–i436 (2016). (PMID: 10.1093/bioinformatics/btw438) Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B Methodol 57, 289–300 (1995). Silva, J. C., Gorenstein, M. V., Li, G.-Z., Vissers, J. P. C. & Geromanos, S. J. Absolute quantification of proteins by LCMSE: a virtue of parallel MS acquisition. Mol. Cell. Proteomics 5, 144–156 (2006). (PMID: 10.1074/mcp.M500230-MCP200) Eden, E., Navon, R., Steinfeld, I., Lipson, D. & Yakhini, Z. GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics 10, 48 (2009). (PMID: 10.1186/1471-2105-10-48) Eden, E., Lipson, D., Yogev, S. & Yakhini, Z. Discovering motifs in ranked lists of DNA sequences. PLoS Comput. Biol. 3, e39 (2007). (PMID: 10.1371/journal.pcbi.0030039) Ruepp, A. et al. CORUM: the comprehensive resource of mammalian protein complexes. Nucleic Acids Res. 36, D646–D650 (2008). (PMID: 10.1093/nar/gkm936) Ruepp, A. et al. CORUM: the comprehensive resource of mammalian protein complexes—2009. Nucleic Acids Res. 38, D497–D501 (2010). (PMID: 10.1093/nar/gkp914) Vinayagam, A. et al. Protein complex-based analysis framework for high-throughput data sets. Sci. Signal. 6, rs5 (2013). (PMID: 10.1126/scisignal.2003629) Ori, A. et al. Spatiotemporal variation of mammalian protein complex stoichiometries. Genome Biol. 17, 47 (2016). (PMID: 10.1186/s13059-016-0912-5) Fuhrer, T., Heer, D., Begemann, B. & Zamboni, N. High-throughput, accurate mass metabolome profiling of cellular extracts by flow injection-time-of-flight mass spectrometry. Anal. Chem. 83, 7074–7080 (2011). (PMID: 10.1021/ac201267k) Wishart, D. S. et al. HMDB 4.0: the human metabolome database for 2018. Nucleic Acids Res. 46, D608–D617 (2018). (PMID: 10.1093/nar/gkx1089) |
المشرفين على المادة: | 0 ((+)-JQ1 compound) 0 (Azepines) 0 (Proteome) 0 (Small Molecule Libraries) 0 (Triazoles) 207SMY3FQT (Vemurafenib) 9647FM7Y3Z (Panobinostat) |
تواريخ الأحداث: | Date Created: 20200122 Date Completed: 20200410 Latest Revision: 20210119 |
رمز التحديث: | 20240628 |
DOI: | 10.1038/s41587-019-0388-4 |
PMID: | 31959954 |
قاعدة البيانات: | MEDLINE |
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