Discovery of novel TAOK2 inhibitor scaffolds from high-throughput screening

Alexander T. Piala, Radha Akella, Malia B. Potts, Stephanie A. Dudics-Giagnocavo, Haixia He, Shuguang Wei, Michael A. White, Bruce A. Posner, Elizabeth J. Goldsmith

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3923-3927
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number16
DOIs
StatePublished - 2016

Fingerprint

Scaffolds
Screening
Phosphotransferases
Throughput
Autophagy
Cells
MAP Kinase Kinase Kinases
MAP Kinase Signaling System
p38 Mitogen-Activated Protein Kinases
Non-Small Cell Lung Carcinoma
Modulators
Cell Line
Molecules
Neoplasms
Therapeutics

Keywords

  • Autophagy
  • Drug discovery
  • High-throughput screening
  • Inhibitor
  • Kinase
  • MAP3K

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Discovery of novel TAOK2 inhibitor scaffolds from high-throughput screening. / Piala, Alexander T.; Akella, Radha; Potts, Malia B.; Dudics-Giagnocavo, Stephanie A.; He, Haixia; Wei, Shuguang; White, Michael A.; Posner, Bruce A.; Goldsmith, Elizabeth J.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 26, No. 16, 2016, p. 3923-3927.

Research output: Contribution to journalArticle

Piala, Alexander T. ; Akella, Radha ; Potts, Malia B. ; Dudics-Giagnocavo, Stephanie A. ; He, Haixia ; Wei, Shuguang ; White, Michael A. ; Posner, Bruce A. ; Goldsmith, Elizabeth J. / Discovery of novel TAOK2 inhibitor scaffolds from high-throughput screening. In: Bioorganic and Medicinal Chemistry Letters. 2016 ; Vol. 26, No. 16. pp. 3923-3927.
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