Ontology highlight
ABSTRACT:
SUBMITTER: Van Dort ME
PROVIDER: S-EPMC4841451 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
Van Dort Marcian E ME Hong Hao H Wang Hanxiao H Nino Charles A CA Lombardi Rachel L RL Blanks Avery E AE Galbán Stefanie S Ross Brian D BD
Journal of medicinal chemistry 20160315 6
The synthesis of a series of single entity, bifunctional MEK1/PI3K inhibitors achieved by covalent linking of structural analogs of the ATP-competitive PI3K inhibitor ZSTK474 and the ATP-noncompetitive MEK inhibitor PD0325901 is described. Inhibitors displayed potent in vitro inhibition of MEK1 (0.015 < IC50 (nM) < 56.7) and PI3K (54 < IC50 (nM) < 341) in enzymatic inhibition assays. Concurrent MEK1 and PI3K inhibition was demonstrated with inhibitors 9 and 14 in two tumor cell lines (A549, D54) ...[more]