su-11248 and midostaurin

su-11248 has been researched along with midostaurin* in 2 studies

Other Studies

2 other study(ies) available for su-11248 and midostaurin

Article	Year
Colony stimulating factor-1 receptor as a target for small molecule inhibitors. Bioorganic & medicinal chemistry, 2010, Mar-01, Volume: 18, Issue:5 Imatinib, dasatinib, sunitinib, CEP-701, and PKC-412, ATP-competitive small molecule inhibitors of type III receptor tyrosine kinases c-KIT and/or FLT3, were evaluated for binding to the closely related receptor, FMS, by docking into models of inactive and active conformations of the FMS kinase domain. To confirm the docking predictions, the drugs were tested for their activity and selectivity in inhibiting cell proliferation and FMS phosphorylation upon stimulation by the FMS ligand, CSF-1. All five drugs inhibited FMS activity. Imatinib, dasatinib and CEP-701 represent three different types of interactions determining drug potency and selectivity. Topics: Benzamides; Binding Sites; Carbazoles; Computer Simulation; Dasatinib; Drug Design; Furans; Humans; Hydrogen Bonding; Imatinib Mesylate; Indoles; Piperazines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Receptor, Macrophage Colony-Stimulating Factor; Staurosporine; Sunitinib; Thiazoles	2010
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood, 2009, Oct-01, Volume: 114, Issue:14 Activating mutations in the receptor tyrosine kinase FLT3 are present in up to approximately 30% of acute myeloid leukemia (AML) patients, implicating FLT3 as a driver of the disease and therefore as a target for therapy. We report the characterization of AC220, a second-generation FLT3 inhibitor, and a comparison of AC220 with the first-generation FLT3 inhibitors CEP-701, MLN-518, PKC-412, sorafenib, and sunitinib. AC220 exhibits low nanomolar potency in biochemical and cellular assays and exceptional kinase selectivity, and in animal models is efficacious at doses as low as 1 mg/kg given orally once daily. The data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties is unique to AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for a clinical FLT3 inhibitor. Topics: Animals; Benzenesulfonates; Benzothiazoles; Bone Marrow; Carbazoles; Cell Line, Tumor; Cell Proliferation; Female; fms-Like Tyrosine Kinase 3; Furans; Humans; Leukemia, Myeloid, Acute; Mice; Mice, Nude; Mice, SCID; Niacinamide; Phenylurea Compounds; Phosphorylation; Piperazines; Prognosis; Protein Interaction Mapping; Protein Kinase C; Protein Kinase Inhibitors; Pyridines; Quinazolines; Sorafenib; Staurosporine; Xenograft Model Antitumor Assays	2009

Article

Year

Colony stimulating factor-1 receptor as a target for small molecule inhibitors.

Bioorganic & medicinal chemistry, 2010, Mar-01, Volume: 18, Issue:5

Imatinib, dasatinib, sunitinib, CEP-701, and PKC-412, ATP-competitive small molecule inhibitors of type III receptor tyrosine kinases c-KIT and/or FLT3, were evaluated for binding to the closely related receptor, FMS, by docking into models of inactive and active conformations of the FMS kinase domain. To confirm the docking predictions, the drugs were tested for their activity and selectivity in inhibiting cell proliferation and FMS phosphorylation upon stimulation by the FMS ligand, CSF-1. All five drugs inhibited FMS activity. Imatinib, dasatinib and CEP-701 represent three different types of interactions determining drug potency and selectivity.

Topics: Benzamides; Binding Sites; Carbazoles; Computer Simulation; Dasatinib; Drug Design; Furans; Humans; Hydrogen Bonding; Imatinib Mesylate; Indoles; Piperazines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Receptor, Macrophage Colony-Stimulating Factor; Staurosporine; Sunitinib; Thiazoles

2010

AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).

Blood, 2009, Oct-01, Volume: 114, Issue:14

Activating mutations in the receptor tyrosine kinase FLT3 are present in up to approximately 30% of acute myeloid leukemia (AML) patients, implicating FLT3 as a driver of the disease and therefore as a target for therapy. We report the characterization of AC220, a second-generation FLT3 inhibitor, and a comparison of AC220 with the first-generation FLT3 inhibitors CEP-701, MLN-518, PKC-412, sorafenib, and sunitinib. AC220 exhibits low nanomolar potency in biochemical and cellular assays and exceptional kinase selectivity, and in animal models is efficacious at doses as low as 1 mg/kg given orally once daily. The data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties is unique to AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for a clinical FLT3 inhibitor.

Topics: Animals; Benzenesulfonates; Benzothiazoles; Bone Marrow; Carbazoles; Cell Line, Tumor; Cell Proliferation; Female; fms-Like Tyrosine Kinase 3; Furans; Humans; Leukemia, Myeloid, Acute; Mice; Mice, Nude; Mice, SCID; Niacinamide; Phenylurea Compounds; Phosphorylation; Piperazines; Prognosis; Protein Interaction Mapping; Protein Kinase C; Protein Kinase Inhibitors; Pyridines; Quinazolines; Sorafenib; Staurosporine; Xenograft Model Antitumor Assays

2009