Discovery of novel TAOK2 inhibitor scaffolds from high-throughput screening.

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Citation

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. Discovery of novel TAOK2 inhibitor scaffolds from high-throughput screening. Bioorganic & medicinal chemistry letters. 2016 Aug 15;26(16):3923-7

PMID: 27426302

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