Inhibition of protein kinases by imatinib
Enzyme . | Substrate phosphorylation IC50 [μM] . | Cellular tyrosine phosphorylation IC50 [μM] . |
|---|---|---|
| c-ABL | 0.2; 0.025* | ND |
| ν-ABL | 0.038 | 0.1-0.3 |
| P210BCR-ABL | 0.025* | 0.25 |
| P185BCR-ABL | 0.025* | 0.25 |
| TEL-ABL | ND | 0.35 |
| PDGF-R α and β | 0.38 (PDGF-Rβ) | 0.1 |
| Tel-PDGF-R | ND | 0.15 |
| c-KIT | 0.41 | 0.1 |
| FLT-3 | > 10 | > 10 |
| Btk | > 10 | ND |
| c-FMS and v-FMS | ND | > 10 |
| c-SRC | > 100 | ND |
| v-SRC | ND | > 10 |
| c-LYN | > 100 | ND |
| c-FGR | > 100 | ND |
| LCK | 9.0 | ND |
| SYK (TPK-IIB) | > 100 | ND |
| JAK-2 | > 100* | > 100 |
| EGF-R | > 100 | > 100 |
| Insulin receptor | > 10 | > 100 |
| IGF-IR | > 10 | > 100 |
| FGF-R1 | 31.2 | ND |
| VEGF-R2 (KDR) | 10.7 | ND |
| VEGF-R1 (FLT-1) | 19.5 | ND |
| VEGF-R3 (FLT-4) | 5.7 | ND |
| TIE-2 (TEK) | > 50 | ND |
| c-MET | > 100 | ND |
| PKA | > 500 | ND |
| PPK | > 500 | ND |
| PKCα, β1, β2, γ, δ, ϵ, ζ, or η | > 100 | ND |
| Protein kinase CK-1, CK-2 | > 100 | ND |
| PKB | > 10 | ND |
| P38 | > 10 | ND |
| PDK1 | > 10 | ND |
| c-Raf-1 | 0.97 | ND |
| CDC2/cyclin B | > 100 | ND |
Enzyme . | Substrate phosphorylation IC50 [μM] . | Cellular tyrosine phosphorylation IC50 [μM] . |
|---|---|---|
| c-ABL | 0.2; 0.025* | ND |
| ν-ABL | 0.038 | 0.1-0.3 |
| P210BCR-ABL | 0.025* | 0.25 |
| P185BCR-ABL | 0.025* | 0.25 |
| TEL-ABL | ND | 0.35 |
| PDGF-R α and β | 0.38 (PDGF-Rβ) | 0.1 |
| Tel-PDGF-R | ND | 0.15 |
| c-KIT | 0.41 | 0.1 |
| FLT-3 | > 10 | > 10 |
| Btk | > 10 | ND |
| c-FMS and v-FMS | ND | > 10 |
| c-SRC | > 100 | ND |
| v-SRC | ND | > 10 |
| c-LYN | > 100 | ND |
| c-FGR | > 100 | ND |
| LCK | 9.0 | ND |
| SYK (TPK-IIB) | > 100 | ND |
| JAK-2 | > 100* | > 100 |
| EGF-R | > 100 | > 100 |
| Insulin receptor | > 10 | > 100 |
| IGF-IR | > 10 | > 100 |
| FGF-R1 | 31.2 | ND |
| VEGF-R2 (KDR) | 10.7 | ND |
| VEGF-R1 (FLT-1) | 19.5 | ND |
| VEGF-R3 (FLT-4) | 5.7 | ND |
| TIE-2 (TEK) | > 50 | ND |
| c-MET | > 100 | ND |
| PKA | > 500 | ND |
| PPK | > 500 | ND |
| PKCα, β1, β2, γ, δ, ϵ, ζ, or η | > 100 | ND |
| Protein kinase CK-1, CK-2 | > 100 | ND |
| PKB | > 10 | ND |
| P38 | > 10 | ND |
| PDK1 | > 10 | ND |
| c-Raf-1 | 0.97 | ND |
| CDC2/cyclin B | > 100 | ND |
Imatinib concentrations causing a 50% reduction in kinase activity (IC50) are given.
PDGF-R indicates platelet-derived growth-factor receptor; ND, not done; Btk, Bruton tyrosine kinase; TPK, tyrosine-protein kinase; EGF-R, epidermal growth-factor receptor; IGF-IR, insulin-like growth factor receptor I, FGF-R1, fibroblast growth factor receptor 1; VEGF-R, vascular endothelial growth factor receptor; PKA, cAMP-dependent protein kinase; PPK, phosphorylase kinase; PKC, protein kinase C; CK, casein kinase; PKB, protein kinase B (also known as Akt); and PKD1, 3-phosphoinoside-dependent protein kinase 1.
IC50 was determined in immunocomplex assays.