title: Phosphorylation State-Dependent High Throughput Screening of the c-Met Kinase.
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.
authors.affiliation: Incyte Corporation, Applied Technology Group, Experimental Station, Route 141 & Henry Clay Road, Wilmington, DE 19880, USA.
authors.forename: Elham
authors.initials: E
authors.lastname: Behshad
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Klabe
authors.forename: Alexander
authors.initials: A
authors.lastname: Margulis
authors.forename: Mary
authors.initials: M
authors.lastname: Becker-Pasha
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Rupar
authors.forename: Paul
authors.initials: P
authors.lastname: Collier
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Liu
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Hollis
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Burn
authors.forename: Richard
authors.initials: R
authors.lastname: Wynn