title: Design, Synthesis, and Characterization of a Photoactivatable Caged Prodrug of Imatinib.
abstract: Imatinib is the first protein kinase inhibitor approved for clinical use and is a seminal drug for the concept of targeted therapy. Herein we report on the design, synthesis, photokinetic properties, and in vitro enzymatic evaluation of a photoactivatable caged prodrug of imatinib. This approach allows spatial and temporal control over the activation of imatinib triggered by ultraviolet light. The successful application of the photoactivation concept to this significant kinase inhibitor provides further evidence for the caging technique as a feasible approach in the kinase field. The presented photoactivatable imatinib prodrug will be highly useful as a pharmacological tool to study the impact of imatinib toward biological systems in greater detail.
authors.affiliation: Christian Albrechts University of Kiel, Institute of Pharmacy, Gutenbergstr. 76, 24118 Kiel (Germany).
authors.forename: Melanie
authors.initials: M
authors.lastname: Zindler
authors.affiliation: Christian Albrechts University of Kiel, Institute of Pharmacy, Gutenbergstr. 76, 24118 Kiel (Germany).
authors.forename: Boris
authors.initials: B
authors.lastname: Pinchuk
authors.affiliation: Christian Albrechts University of Kiel, Institute of Pharmacy, Gutenbergstr. 76, 24118 Kiel (Germany).
authors.forename: Christian
authors.initials: C
authors.lastname: Renn
authors.affiliation: Christian Albrechts University of Kiel, Institute of Pharmacy, Gutenbergstr. 76, 24118 Kiel (Germany).
authors.forename: Rebecca
authors.initials: R
authors.lastname: Horbert
authors.affiliation: Christian Albrechts University of Kiel, Institute of Pharmacy, Gutenbergstr. 76, 24118 Kiel (Germany).
authors.forename: Alexander
authors.initials: A
authors.lastname: Döbber
authors.affiliation: Christian Albrechts University of Kiel, Institute of Pharmacy, Gutenbergstr. 76, 24118 Kiel (Germany). cpeifer@pharmazie.uni-kiel.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Peifer
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D015195:Drug Design; D000068877:Imatinib Mesylate / Q000138:chemical synthesis / Q000737:chemistry*; D062105:Molecular Docking Simulation; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000737:chemistry / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D011355:Prodrugs; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: PDGF-Rβ; caged prodrugs; imatinib; inhibitors; kinases; photoactivation