In vivo Anti-Cancer Activity of a Liposomal Nanoparticle Construct of Multifunctional Tyrosine Kinase Inhibitor 4-(4’-Hydroxyphenyl)-Amino-6,7-Dimethoxyquinazoline
نویسندگان
چکیده
Developmental Therapeutics Program, Institute for Pediatric Clinical Research, Children’s Hospital Los Angeles & Division of Hematology-Oncology, Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA Molecular Oncology and Drug Discovery Program, Parker Hughes Institute, P.O Box 130366, St. Paul, MN 55113-0004, USA Department of Biology, Gustavus Adolphus College, 800 W College Avenue, St. Peter, MN 56082, USA
منابع مشابه
Structure-based design of specific inhibitors of Janus kinase 3 as apoptosis-inducing antileukemic agents.
A novel homology model of the kinase domain of Janus kinase (JAK) 3 was used for the structure-based design of dimethoxyquinazoline compounds with potent and specific inhibitory activity against JAK3. The active site of JAK3 in this homology model measures roughly 8 A x 11 A x 20 A, with a volume of approximately 530 A3 available for inhibitor binding. Modeling studies indicated that 4-(phenyl)...
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4-(3',5'-Dibromo-4'-hydroxyphenyl)amino-6,7-dimethoxyquinazoline (WHI-P97) is a rationally designed potent inhibitor of Janus kinase (JAK)-3. Treatment of mast cells with WHI-P97 inhibited the translocation of 5-lipoxygenase (5-LO) from the nucleoplasm to the nuclear membrane and consequently 5-LO-dependent leukotriene (LT) synthesis after IgE receptor/FcepsilonRI crosslinking by >90% at low mi...
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Here we report the phase I metabolism of the rationally designed Janus kinase-3 (JAK) inhibitor 4-(4'-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131; JANEX-1). JANEX-1 was metabolized by the cytochrome P450 enzymes CYP1A1 and CYP1A2 in a regioselective fashion to form the biologically inactive 7-O-demethylation product 4-(4'-hydroxyphenyl)-amino-6-methoxy-7-hydroxyquinazoline (JANEX-1-...
متن کاملA Novel Quinazoline Derivative with Potent Cytotoxic Activity against Human Glioblastoma Cells
The novel quinazoline derivative 4-(3’-bromo-4’hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHIP154) exhibited significant cytotoxicity against U373 and U87 human glioblastoma cell lines, causing apoptotic cell death at micromolar concentrations. The in vitro antiglioblastoma activity of WHI-P154 was amplified >200-fold and rendered selective by conjugation to recombinant human epidermal gro...
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Adenosine and acetylcholine (ACh) trigger preconditioning through different signaling pathways. We tested whether either could activate myocardial phosphatidylinositol 3-kinase (PI3-kinase), a putative signaling protein in ischemic preconditioning. We used phosphorylation of Akt, a downstream target of PI3-kinase, as a reporter. Exposure of isolated rabbit hearts to ACh increased Akt phosphoryl...
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