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  1. AU="Leibrock, Lea"
  2. AU="Dubrovskiĭ, I A"
  3. AU="Thomaz, Natalie K"
  4. AU="Ahmed, Mostafa S."
  5. AU="Im, Kate"
  6. AU="Ben Mustapha, Nadia"
  7. AU="Yokoyama, Yukihiro"
  8. AU="Zhu, Yu Peng"
  9. AU="Rbia, Nadia"
  10. AU="Wile, Rachel K"
  11. AU="Vallejo, Jesús G"
  12. AU="Tarantino, Lisa M."
  13. AU="Desidério Favarato"
  14. AU=Becker Stefan
  15. AU=Siddiquie Reshma Y.
  16. AU="Ounajim, Amine"
  17. AU=Clothier Hazel J
  18. AU="Ting, Kang"
  19. AU="Bitèye, Omar"
  20. AU="Koch, Cornelia"
  21. AU="Białecki, Piotr"
  22. AU="Taylor, Maureen E"
  23. AU="Karpov, M."
  24. AU="Vogel Gonzalez, M"
  25. AU="Montevecchi, William A"
  26. AU="Vanhoni, Laura Rassi"
  27. AU="Atkins, Kristen A"
  28. AU="Sun, Zhenyu J"
  29. AU="Boton, Noah H"
  30. AU=Anderson Claire
  31. AU="Pielmus, Alexandru-Gabriel"
  32. AU="Neacsu, Ionela Andreea"
  33. AU=Keller Ray
  34. AU="Gopas, Jacob"
  35. AU="Berthelson, P R"
  36. AU="Rivera-Torres, Juan J"
  37. AU="Henriquez, Javier"
  38. AU="Adele N Burgess"
  39. AU="Spencer T. Plumb"

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  1. Article ; Online: Development of High Brain-Penetrant and Reversible Monoacylglycerol Lipase PET Tracers for Neuroimaging.

    He, Yingfang / Schild, Matthias / Grether, Uwe / Benz, Jörg / Leibrock, Lea / Heer, Dominik / Topp, Andreas / Collin, Ludovic / Kuhn, Bernd / Wittwer, Matthias / Keller, Claudia / Gobbi, Luca C / Schibli, Roger / Mu, Linjing

    Journal of medicinal chemistry

    2022  Volume 65, Issue 3, Page(s) 2191–2207

    Abstract: Monoacylglycerol lipase (MAGL) is one of the key enzymes in the endocannabinoid system. Inhibition of MAGL has been proposed as an attractive approach for the treatment of various diseases. In this study, we designed and successfully synthesized two ... ...

    Abstract Monoacylglycerol lipase (MAGL) is one of the key enzymes in the endocannabinoid system. Inhibition of MAGL has been proposed as an attractive approach for the treatment of various diseases. In this study, we designed and successfully synthesized two series of piperazinyl pyrrolidin-2-one derivatives as novel reversible MAGL inhibitors. (
    MeSH term(s) Animals ; Brain/diagnostic imaging ; Brain/metabolism ; Carbon Radioisotopes/chemistry ; Crystallography, X-Ray ; Drug Stability ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/metabolism ; Enzyme Inhibitors/pharmacokinetics ; Mice ; Molecular Conformation ; Monoacylglycerol Lipases/chemistry ; Monoacylglycerol Lipases/metabolism ; Neuroimaging/methods ; Positron-Emission Tomography ; Radiopharmaceuticals/chemistry ; Radiopharmaceuticals/metabolism ; Radiopharmaceuticals/pharmacokinetics ; Rats ; Rats, Wistar ; Structure-Activity Relationship ; Tissue Distribution
    Chemical Substances Carbon Radioisotopes ; Carbon-11 ; Enzyme Inhibitors ; Radiopharmaceuticals ; Monoacylglycerol Lipases (EC 3.1.1.23)
    Language English
    Publishing date 2022-01-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.1c01706
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Format chain exchange (FORCE) for high-throughput generation of bispecific antibodies in combinatorial binder-format matrices.

    Dengl, Stefan / Mayer, Klaus / Bormann, Felix / Duerr, Harald / Hoffmann, Eike / Nussbaum, Bianca / Tischler, Michael / Wagner, Martina / Kuglstatter, Andreas / Leibrock, Lea / Buldun, Can / Georges, Guy / Brinkmann, Ulrich

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 4974

    Abstract: Generation of bispecific antibodies (bsAbs) requires a combination of compatible binders in formats that support desired functionalities. Here, we report that bsAb-matrices can be generated by Format Chain Exchange (FORCE), enabling screening of ... ...

    Abstract Generation of bispecific antibodies (bsAbs) requires a combination of compatible binders in formats that support desired functionalities. Here, we report that bsAb-matrices can be generated by Format Chain Exchange (FORCE), enabling screening of combinatorial binder/format spaces. Input molecules for generation of bi/multi-valent bsAbs are monospecific entities similar to knob-into-hole half-antibodies, yet with complementary CH3-interface-modulated and affinity-tagged dummy-chains. These contain mutations that lead to limited interface repulsions without compromising expression or biophysical properties of educts. Mild reduction of combinations of educts triggers spontaneous chain-exchange reactions driven by partially flawed CH3-educt interfaces resolving to perfect complementarity. This generates large bsAb matrices harboring different binders in multiple formats. Benign biophysical properties and good expression yields of educts, combined with simplicity of purification enables process automation. Examples that demonstrate the relevance of screening binder/format combinations are provided as a matrix of bsAbs that simultaneously bind Her1/Her2 and DR5 without encountering binder or format-inflicted interferences.
    MeSH term(s) Antibodies, Bispecific/biosynthesis ; Antibodies, Bispecific/isolation & purification ; Automation ; HEK293 Cells ; High-Throughput Screening Assays ; Humans ; Mutation/genetics ; Protein Multimerization
    Chemical Substances Antibodies, Bispecific
    Language English
    Publishing date 2020-10-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-18477-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: CD25-T

    Solomon, Isabelle / Amann, Maria / Goubier, Anne / Arce Vargas, Frederick / Zervas, Dimitrios / Qing, Chen / Henry, Jake Y / Ghorani, Ehsan / Akarca, Ayse U / Marafioti, Teresa / Śledzińska, Anna / Werner Sunderland, Mariana / Franz Demane, Dafne / Clancy, Joanne Ruth / Georgiou, Andrew / Salimu, Josephine / Merchiers, Pascal / Brown, Mark Adrian / Flury, Reto /
    Eckmann, Jan / Murgia, Claudio / Sam, Johannes / Jacobsen, Bjoern / Marrer-Berger, Estelle / Boetsch, Christophe / Belli, Sara / Leibrock, Lea / Benz, Joerg / Koll, Hans / Sutmuller, Roger / Peggs, Karl S / Quezada, Sergio A

    Nature cancer

    2020  Volume 1, Issue 12, Page(s) 1153–1166

    Abstract: Intratumoral regulatory T cell (Treg) abundance associates with diminished anti-tumor immunity and poor prognosis in human cancers. Recent work demonstrates that CD25, the high affinity receptor subunit for IL-2, is a selective target for Treg depletion ... ...

    Abstract Intratumoral regulatory T cell (Treg) abundance associates with diminished anti-tumor immunity and poor prognosis in human cancers. Recent work demonstrates that CD25, the high affinity receptor subunit for IL-2, is a selective target for Treg depletion in mouse and human malignancies; however, anti-human CD25 antibodies have failed to deliver clinical responses against solid tumors due to bystander IL-2 receptor signaling blockade on effector T cells, which limits their anti-tumor activity. Here we demonstrate potent single-agent activity of anti-CD25 antibodies optimized to deplete Tregs whilst preserving IL-2-STAT5 signaling on effector T cells, and demonstrate synergy with immune checkpoint blockade in vivo. Pre-clinical evaluation of an anti-human CD25 (RG6292) antibody with equivalent features demonstrates, in both non-human primates and humanized mouse models, efficient Treg depletion with no overt immune-related toxicities. Our data supports the clinical development of RG6292 and evaluation of novel combination therapies incorporating non-IL-2 blocking anti-CD25 antibodies in clinical studies.
    MeSH term(s) Animals ; Antibodies, Monoclonal/pharmacology ; Interleukin-2/pharmacology ; Mice ; Neoplasms ; Signal Transduction ; T-Lymphocytes, Regulatory
    Chemical Substances Antibodies, Monoclonal ; Interleukin-2
    Language English
    Publishing date 2020-11-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2662-1347
    ISSN (online) 2662-1347
    DOI 10.1038/s43018-020-00133-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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