Design, synthesis, and functional evaluation of triazine-based bivalent agents that simultaneously target the active site and hot spot of phosphatase ...
Basic Information
ID: ALA4823292
Journal: Bioorg Med Chem Lett
Title: Design, synthesis, and functional evaluation of triazine-based bivalent agents that simultaneously target the active site and hot spot of phosphatase Cdc25B.
Authors: Nagaoka Y, Parvatkar P, Hirai G, Ohkanda J.
Abstract: Cdc25B phosphatase catalyzes the dephosphorylation and activation of cyclin-dependent kinases 2 (CDK2/CycA) and their overexpression has been reported in cancers. Although Cdc25B has received much attention as a drug target, its flat and featureless surface makes it challenging to develop new agents targeting this protein. In this study, we investigated the rational design of a series of bivalent triazine-based derivatives with the aim of simultaneously targeting the active site and the remote hotspot critical for the interaction with CDK2/CycA. Compounds 1e and 10, containing aromatic residues, were shown to inhibit Cdc25B activity selectively over Cdc25A at low micromolar concentration.
CiteXplore: 34273487
DOI: 10.1016/j.bmcl.2021.128265
Patent ID: ┄