{"entity": "publication", "iuid": "10ef60b326fc4a40a475a5da7395af74", "timestamp": "2026-05-09T17:13:49.250Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/10ef60b326fc4a40a475a5da7395af74.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/10ef60b326fc4a40a475a5da7395af74"}}, "title": "Optimization of an Imidazo[1,2-a]pyridine Series to Afford Highly Selective Type I1/2 Dual Mer/Axl Kinase Inhibitors with In Vivo Efficacy.", "authors": [{"family": "McCoull", "given": "William", "initials": "W", "orcid": "0000-0002-2977-1744", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6bc793ab67054ee184178aca4d8b362e.json"}}, {"family": "Boyd", "given": "Scott", "initials": "S"}, {"family": "Brown", "given": "Martin R", "initials": "MR"}, {"family": "Coen", "given": "Muireann", "initials": "M"}, {"family": "Collingwood", "given": "Olga", "initials": "O"}, {"family": "Davies", "given": "Nichola L", "initials": "NL"}, {"family": "Doherty", "given": "Ann", "initials": "A"}, {"family": "Fairley", "given": "Gary", "initials": "G"}, {"family": "Goldberg", "given": "Kristin", "initials": "K"}, {"family": "Hardaker", "given": "Elizabeth", "initials": "E"}, {"family": "He", "given": "Guang", "initials": "G"}, {"family": "Hennessy", "given": "Edward J", "initials": "EJ"}, {"family": "Hopcroft", "given": "Philip", "initials": "P"}, {"family": "Hodgson", "given": "George", "initials": "G"}, {"family": "Jackson", "given": "Anne", "initials": "A"}, {"family": "Jiang", "given": "Xiefeng", "initials": "X"}, {"family": "Karmokar", "given": "Ankur", "initials": "A"}, {"family": "Lain\u00e9", "given": "Anne-Laure", "initials": "AL"}, {"family": "Lindsay", "given": "Nicola", "initials": "N"}, {"family": "Mao", "given": "Yumeng", "initials": "Y"}, {"family": "Markandu", "given": "Roshini", "initials": "R"}, {"family": "McMurray", "given": "Lindsay", "initials": "L"}, {"family": "McLean", "given": "Neville", "initials": "N"}, {"family": "Mooney", "given": "Lorraine", "initials": "L"}, {"family": "Musgrove", "given": "Helen", "initials": "H"}, {"family": "Nissink", "given": "J Willem M", "initials": "JWM", "orcid": "0000-0003-2572-9140", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb258b6d5f2c4f3c88bdbe44752a6704.json"}}, {"family": "Pflug", "given": "Alexander", "initials": "A"}, {"family": "Reddy", "given": "Venkatesh Pilla", "initials": "VP"}, {"family": "Rawlins", "given": "Philip B", "initials": "PB"}, {"family": "Rivers", "given": "Emma", "initials": "E"}, {"family": "Schimpl", "given": "Marianne", "initials": "M", "orcid": "0000-0003-2284-5250", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ceffc902e4d44abbbaa73f0d1a9a562.json"}}, {"family": "Smith", "given": "Graham F", "initials": "GF"}, {"family": "Tentarelli", "given": "Sharon", "initials": "S", "orcid": "0000-0003-2968-8120", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ad0b1650fc3a45738b22ac63b24c3482.json"}}, {"family": "Travers", "given": "Jon", "initials": "J"}, {"family": "Troup", "given": "Robert I", "initials": "RI"}, {"family": "Walton", "given": "Josephine", "initials": "J"}, {"family": "Wang", "given": "Cheng", "initials": "C"}, {"family": "Wilkinson", "given": "Stephen", "initials": "S"}, {"family": "Williamson", "given": "Beth", "initials": "B"}, {"family": "Winter-Holt", "given": "Jon", "initials": "J"}, {"family": "Yang", "given": "Dejian", "initials": "D"}, {"family": "Zheng", "given": "Yuting", "initials": "Y"}, {"family": "Zhu", "given": "Qianxiu", "initials": "Q"}, {"family": "Smith", "given": "Paul D", "initials": "PD"}], "type": "journal article", "published": "2021-09-23", "journal": {"title": "J Med Chem", "issn": "1520-4804", "volume": "64", "issue": "18", "pages": "13524-13539", "issn-l": "0022-2623"}, "abstract": "Inhibition of Mer and Axl kinases has been implicated as a potential way to improve the efficacy of current immuno-oncology therapeutics by restoring the innate immune response in the tumor microenvironment. Highly selective dual Mer/Axl kinase inhibitors are required to validate this hypothesis. Starting from hits from a DNA-encoded library screen, we optimized an imidazo[1,2-a]pyridine series using structure-based compound design to improve potency and reduce lipophilicity, resulting in a highly selective in vivo probe compound 32. We demonstrated dose-dependent in vivo efficacy and target engagement in Mer- and Axl-dependent efficacy models using two structurally differentiated and selective dual Mer/Axl inhibitors. Additionally, in vivo efficacy was observed in a preclinical MC38 immuno-oncology model in combination with anti-PD1 antibodies and ionizing radiation.", "doi": "10.1021/acs.jmedchem.1c00920", "pmid": "34478292", "labels": {"SciLifeLab Fellow": null, "Yumeng Mao": null}, "xrefs": [], "notes": [], "created": "2023-05-12T11:53:11.235Z", "modified": "2023-05-12T11:53:11.371Z"}