2. Academic Validation
  3. Discovery of a Highly Selective Tankyrase Inhibitor Displaying Growth Inhibition Effects against a Diverse Range of Tumor Derived Cell Lines

Discovery of a Highly Selective Tankyrase Inhibitor Displaying Growth Inhibition Effects against a Diverse Range of Tumor Derived Cell Lines

  • J Med Chem. 2017 Jul 13;60(13):5455-5471. doi: 10.1021/acs.jmedchem.7b00137.
Douglas W Thomson 1,  Anne J Wagner 1,  Marcus Bantscheff 1,  R Edward Benson 2,  Lars Dittus 1,  Birgit Duempelfeld 1,  Gerard Drewes 1,  Jana Krause 1,  John T Moore 2,  Katrin Mueller 1,  Daniel Poeckel 1,  Christina Rau 1,  Elsa Salzer 1,  Lisa Shewchuk 3,  Carsten Hopf 1,  John G Emery 4,  Marcel Muelbaier 1
Affiliations

Affiliations

  • 1 Cellzome GmbH, A GlaxoSmithKline Company , Meyerhofstraße 1, 69117 Heidelberg, Germany.
  • 2 GlaxoSmithKline , Research Triangle Park, 5 Moore Drive, North Carolina 27709, United States.
  • 3 Protein, Cellular & Structural Sciences, GlaxoSmithKline , 1250 South Collegeville Road, Upper Providence, Pennsylvania 19426, United States.
  • 4 Virtual Proof of Concept DPU, GlaxoSmithKline , 709 Swedeland Road, King of Prussia, Pennsylvania 19406, United States.
PMID: 28591512 DOI: 10.1021/acs.jmedchem.7b00137
Abstract

The availability of high quality probes for specific protein targets is fundamental to the investigation of their function and their validation as therapeutic targets. We report the utilization of a dedicated chemoproteomic assay platform combining affinity enrichment technology with high-resolution protein mass spectrometry to the discovery of a novel nicotinamide isoster, the tetrazoloquinoxaline 41, a highly potent and selective tankyrase inhibitor. We also describe the use of 41 to investigate the biology of tankyrase, revealing the compound induced growth inhibition of a number of tumor derived cell lines, demonstrating the potential of tankyrase inhibitors in oncology.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-117700
    TNKS Inhibitor