2. Academic Validation
  3. Discovery of novel TAOK2 inhibitor scaffolds from high-throughput screening

Discovery of novel TAOK2 inhibitor scaffolds from high-throughput screening

  • Bioorg Med Chem Lett. 2016 Aug 15;26(16):3923-7. doi: 10.1016/j.bmcl.2016.07.016.
Alexander T Piala 1,  Radha Akella 1,  Malia B Potts 2,  Stephanie A Dudics-Giagnocavo 2,  Haixia He 1,  Shuguang Wei 3,  Michael A White 2,  Bruce A Posner 3,  Elizabeth J Goldsmith 4
Affiliations

Affiliations

  • 1 Department of Biophysics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8816, United States.
  • 2 Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8816, United States.
  • 3 Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8816, United States.
  • 4 Department of Biophysics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8816, United States. Electronic address: [email protected].
PMID: 27426302 DOI: 10.1016/j.bmcl.2016.07.016
Abstract

The MAP3K (Mitogen Activated Protein Kinase Kinase Kinase) TAOK2 (Thousand-And-One Kinase 2) is an activator of p38 MAP kinase cascade that is up-regulated in response to environmental stresses. A synthetic lethal screen performed using a NSCLC (non-small cell lung Cancer) cell line, and a second screen identifying potential modulators of Autophagy have implicated TAOK2 as a potential Cancer therapeutic target. Using a 200,000 compound high throughput screen, we identified three specific small molecule compounds that inhibit the kinase activity of TAOK2. These compounds also showed inhibition of Autophagy. Based on SAR (structure-activity relationship) studies, we have predicted the modifications on the reactive groups for the three compounds.

Keywords

Autophagy; Drug discovery; High-throughput screening; Inhibitor; Kinase; MAP3K.

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