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1.	Al-Amin, Rasel A., Researcher, 1983-, et al. (author) Monitoring drug–target interactions through target engagement-mediated amplification on arrays and in situ 2022 In: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 50:22, s. e129-e129 Journal article (peer-reviewed)abstract Drugs are designed to bind their target proteins in physiologically relevant tissues and organs to modulate biological functions and elicit desirable clinical outcomes. Information about target engagement at cellular and subcellular resolution is therefore critical for guiding compound optimization in drug discovery, and for probing resistance mechanisms to targeted therapies in clinical samples. We describe a target engagement-mediated amplification (TEMA) technology, where oligonucleotide-conjugated drugs are used to visualize and measure target engagement in situ, amplified via rolling-circle replication of circularized oligonucleotide probes. We illustrate the TEMA technique using dasatinib and gefitinib, two kinase inhibitors with distinct selectivity profiles. In vitro binding by the dasatinib probe to arrays of displayed proteins accurately reproduced known selectivity profiles, while their differential binding to fixed adherent cells agreed with expectations from expression profiles of the cells. We also introduce a proximity ligation variant of TEMA to selectively investigate binding to specific target proteins of interest. This form of the assay serves to improve resolution of binding to on- and off-target proteins. In conclusion, TEMA has the potential to aid in drug development and clinical routine by conferring valuable insights in drug–target interactions at spatial resolution in protein arrays, cells and in tissues.
2.	Golob-Schwarzl, N., et al. (author) Correction: High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype12 (vol 12, pg 256, 2019) 2020 In: Translational Oncology. - : ELSEVIER SCIENCE INC. - 1944-7124 .- 1936-5233. ; 13:2, s. 490-492 Journal article (other academic/artistic)abstract n/a

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Type of publication: journal article (2)

Type of content: other academic/artistic (1); peer-reviewed (1)

Author/Editor: Haybaeck, Johannes (2); Johansson, Lars (1); Chen, X. (1); Mueller, H. (1); Nilsson, Peter (1); Abdurakhmanov, Eldar ... (1); show more...; Landegren, Nils, 198 ... (1); Landegren, Ulf (1); Kamali-Moghaddam, Ma ... (1); Artursson, Per (1); Al-Amin, Rasel A., R ... (1); Löf, Liza (1); Arngården, Linda, 19 ... (1); Blokzijl, Andries (1); Svensson, Richard (1); Hammond, Maria, 1984 ... (1); Lönn, Peter (1); Jenmalm Jensen, Anni ... (1); Danielson, U. Helena ... (1); Lundbäck, Thomas (1); Hoshida, Y (1); Stojakovic, T (1); Thueringer, A (1); Stumptner, C (1); Strnad, P (1); Golob-Schwarzl, N. (1); Bettermann, K. (1); Mehta, A. K. (1); Kessler, S. M. (1); Unterluggauer, J. (1); Krassnig, S. (1); Kojima, K. (1); Bardeesy, N. M. (1); Svendova, V. (1); Schimek, M. G. (1); Diwoky, C. (1); Lipfert, A. (1); Mahajan, V. (1); Frohlich, L. F. (1); Kolbe, T. (1); Ruelicke, T. (1); Magin, T. M. (1); Kiemer, A. K. (1); Moriggl, R. (1); show less...

University: Uppsala University (1); Linköping University (1); Karolinska Institutet (1)

Language: English (2)

Research subject (UKÄ/SCB): Natural sciences (1); Medical and Health Sciences (1)

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