Inhibitory activity of SU5614 against different protein tyrosine kinases
Protein tyrosine kinase . | IC50, μM . | |
---|---|---|
Kinase assay . | Biologic assay . | |
FLT3 | ND | — |
Growth arrest | — | 0.45 |
Apoptosis | — | 0.65 |
Dephosphorylation of FLT3 | — | 0.15 |
KIT | 0.03 | 0.2 |
VEGFR-2/VEGF | 0.46 | 0.07 |
PDGFRβ/PDGF | 0.36 | 0.5 |
FMS | 13 | ND |
EGFR/EGF | > 100 | > 100 |
FGFR-1/FGF | > 100 | > 50 |
TEL-ABL/BCR-ABL | ND | > 10 |
TEL-JAK2 | ND | > 10 |
Protein tyrosine kinase . | IC50, μM . | |
---|---|---|
Kinase assay . | Biologic assay . | |
FLT3 | ND | — |
Growth arrest | — | 0.45 |
Apoptosis | — | 0.65 |
Dephosphorylation of FLT3 | — | 0.15 |
KIT | 0.03 | 0.2 |
VEGFR-2/VEGF | 0.46 | 0.07 |
PDGFRβ/PDGF | 0.36 | 0.5 |
FMS | 13 | ND |
EGFR/EGF | > 100 | > 100 |
FGFR-1/FGF | > 100 | > 50 |
TEL-ABL/BCR-ABL | ND | > 10 |
TEL-JAK2 | ND | > 10 |
In biologic assays, the concentration of SU5614 that inhibits 50% growth of MM6 or TEL-ABL/TEL-JAK2–transduced Ba/F3 cells after an incubation period of 72 hours was determined (IC50). The concentration of SU5614 that induces apoptosis in 50% of MM6 cells after a 48-hour incubation period or that induces a 50% dephosphorylation of FLT3 in MM6 cells after an incubation time of 3 hours was defined as the IC50. The autophosphorylation of FLT3 was measured in intact cells by antiphosphotyrosine antibody after immunoprecipitation with FLT3 antibody and the IC50was calculated by densitometry. To determine the IC50 of SU5614 against KIT, Kasumi-1 cells that express high levels of KIT and show a cytokine-dependent growth were used. The concentration of SU5614 that inhibits 50% growth in Kasumi-1 cells after an incubation period of 72 hours was determined (IC50) as described previously.28 The IC50 values of SU5614 against VEGFR-2, KIT, PDGFR, FMS, EGFR, and FGFR as determined in kinase assays and in biologic assays have been described previously and are reproduced with the permission of the publisher and the authors.46
FGF indicates fibroblast growth factor; FGFR, fibroblast growth factor receptor; ND, not determined; —, not applicable.