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Behshad E, Klabe RM, Margulis A, et al. Phosphorylation State-Dependent High Throughput Screening of the c-Met Kinase. Curr Chem Genomics. 2010;4:27-33doi: 10.2174/1875397301004010027.
Behshad, E., Klabe, R. M., Margulis, A., Becker-Pasha, M., Rupar, M. J., Collier, P., Liu, P. C., Hollis, G. F., Burn, T. C., & Wynn, R. (2010). Phosphorylation State-Dependent High Throughput Screening of the c-Met Kinase. Current chemical genomics, 427-33. https://doi.org/10.2174/1875397301004010027
Behshad, Elham, et al. "Phosphorylation State-Dependent High Throughput Screening of the c-Met Kinase." Current chemical genomics vol. 4 (2010): 27-33. doi: https://doi.org/10.2174/1875397301004010027
Behshad E, Klabe RM, Margulis A, Becker-Pasha M, Rupar MJ, Collier P, Liu PC, Hollis GF, Burn TC, Wynn R. Phosphorylation State-Dependent High Throughput Screening of the c-Met Kinase. Curr Chem Genomics. 2010 Apr 23;4:27-33. doi: 10.2174/1875397301004010027. PMID: 20556206; PMCID: PMC2885599.
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Curr Chem Genomics. 2010 Apr 23;4:27-33. doi: 10.2174/1875397301004010027.

Phosphorylation State-Dependent High Throughput Screening of the c-Met Kinase.

Current chemical genomics

Elham Behshad, Ronald M Klabe, Alexander Margulis, Mary Becker-Pasha, Mark J Rupar, Paul Collier, Phillip C Liu, Gregory F Hollis, Timothy C Burn, Richard Wynn

Affiliations

  1. Incyte Corporation, Applied Technology Group, Experimental Station, Route 141 & Henry Clay Road, Wilmington, DE 19880, USA.

PMID: 20556206 PMCID: PMC2885599 DOI: 10.2174/1875397301004010027

Abstract

High-throughput screening (HTS) of ~50,000 chemical compounds against phosphorylated and unphosphorylated c-Met, a tyrosine kinase receptor for hepatocyte growth factor (HGF), was carried out in order to compare hit rates, hit potencies and also to explore scaffolds that might serve as potential leads targeting only the unphosphorylated form of the enzyme. The hit rate and potency for the confirmed hit molecules were higher for the unphosphoryalted form of c-Met. While the target of small molecule inhibitor discovery efforts has traditionally been the phosphorylated form, there are now examples of small molecules that target unphosphorylated kinases. Screening for inhibitors of unphosphorylated kinases may represent a complementary approach for prioritizing chemical scaffolds for hit-to-lead follow ups.

Keywords: HTRF; Kinase; c-Met; cancer.; high throughput screening; phosphorylation

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