2. Academic Validation
  3. Highly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core

Highly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core

  • Eur J Med Chem. 2021 Apr 5:215:113299. doi: 10.1016/j.ejmech.2021.113299.
Václav Němec 1,  Lukáš Maier 1,  Benedict-Tilman Berger 2,  Apirat Chaikuad 2,  Stanislav Drápela 3,  Karel Souček 3,  Stefan Knapp 2,  Kamil Paruch 4
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic; International Clinical Research Center, Center for Biomolecular and Cellular Engineering, St. Anne's University Hospital in Brno, Pekařská 53, 656 91, Brno, Czech Republic.
  • 2 Structural Genomics Consortium (SGC), Buchmann Institute for Life Sciences (BMLS), Goethe University Frankfurt am Main, Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany; Institut für Pharmazeutische Chemie, Goethe University Frankfurt am Main, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany.
  • 3 International Clinical Research Center, Center for Biomolecular and Cellular Engineering, St. Anne's University Hospital in Brno, Pekařská 53, 656 91, Brno, Czech Republic; Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65, Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Kotlářská 267/2, 611 37, Brno, Czech Republic.
  • 4 Department of Chemistry, Faculty of Science, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic; International Clinical Research Center, Center for Biomolecular and Cellular Engineering, St. Anne's University Hospital in Brno, Pekařská 53, 656 91, Brno, Czech Republic. Electronic address: paruch@chemi.muni.cz.
PMID: 33636538 DOI: 10.1016/j.ejmech.2021.113299
Abstract

The furo [3,2-b]pyridine motif represents a relatively underexplored central pharmacophore in the area of kinase inhibitors. Herein, we report flexible synthesis of 3,5-disubstituted furo [3,2-b]pyridines that relies on chemoselective couplings of newly prepared 5-chloro-3-iodofuro [3,2-b]pyridine. This methodology allowed efficient second-generation synthesis of the state-of-the-art chemical biology probe for CLK1/2/4 MU1210, and identification of the highly selective inhibitors of HIPKs MU135 and MU1787 which are presented and characterized in this study, including the X-ray crystal structure of MU135 in HIPK2. chemical biology probe.

Keywords

CLK; Furo[3,2-b]pyridine; HIPK; Inhibitor; Kinase; MU1210; MU135; MU1787.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-177416
    HIPK Inhibitor