Table 2. A list of kinases that are inhibited (>50%) by bosutinib and dasatinib as determined by in vitro profiling.
| Kinases inhibited >50% by Bos-I | Kinases inhibited >50% by Dasatinib | ||||
|---|---|---|---|---|---|
| Kinase | % Residual activity | Kinase | % Residual activity | ||
| ABL1 | 1.8 | ABL1 | 2.77 | ||
| ABL2/ARG | 2.19 | ABL2/ARG | 2.74 | ||
| ACK1 | 3.54 | ACK1 | 2.62 | ||
| ARK5/NUAK1 | 11.43 | ALK1/ACVRL1 | 15.93 | ||
| AXL | 37.63 | ARAF | 33.76 | ||
| BLK | 20.73 | BLK | 3.04 | ||
| BMX/ETK | 14.48 | BMX/ETK | 2.53 | ||
| BTK | 5.69 | BRK | 4.59 | ||
| CAMK1d | 16.57 | BTK | 2.09 | ||
| CHK1 | 38.9 | c-Kit | 3.27 | ||
| CHK2 | 21.7 | CSK | 7.11 | ||
| CK1d | 10.86 | c-SRC | 3.52 | ||
| CK1epsilon | 11.44 | DDR2 | 0.24 | ||
| c-MER | 28.92 | EGFR | 21.08 | ||
| CSK | 12.33 | EPHA1 | 2.72 | ||
| c-SRC | 6.05 | EPHA2 | 6.82 | ||
| EGFR | 3.84 | EPHA3 | 3.46 | ||
| EPHA2 | 9.58 | EPHA4 | 1.63 | ||
| EPHA3 | 31.66 | EPHA5 | 0.24 | ||
| EPHA4 | 27.01 | EPHA8 | 4.13 | ||
| EPHA5 | 37.14 | EPHB1 | 4.8 | ||
| EPHA6 | 4.38 | EPHB2 | 0 | ||
| EPHA8 | 10.52 | EPHB3 | 0.99 | ||
| EPHB1 | 11.8 | EPHB4 | 1.17 | ||
| EPHB2 | 17.43 | ERBB4/HER4 | 4.03 | ||
| EPHB3 | 49.42 | FGR | 1.7 | ||
| EPHB4 | 12.48 | FMS | 0.77 | ||
| ERBB2/HER2 | 32.95 | FRK/PTK5 | 0 | ||
| ERBB4/HER4 | 1.53 | FYN | 1.96 | ||
| FES/FPS | 35.71 | HCK | 0.79 | ||
| FGR | 11.49 | HGK MAP4K4 | 49.2 | ||
| FLT1/VEGFR1 | 44.54 | KHS MAP4K5 | 3.07 | ||
| FLT3 | 30.26 | LCK | 0.31 | ||
| FLT4/VEGFR3 | 44.1 | LIMK1 | 16.71 | ||
| FMS | 43.09 | LYN | 0.43 | ||
| FRK/PTK5 | 29.2 | LYN B | 1.6 | ||
| FYN | 29.42 | MINK/MINK1 | 46.54 | ||
| GCK MAP4K2 | 3.16 | NEK11 | 21.66 | ||
| HCK | 11.88 | NLK | 27.49 | ||
| HGK MAP4K4 | 1.03 | P38a/MAPK14 | 36.53 | ||
| IRR/INSRR | 36.9 | PDGFRa | 1.82 | ||
| KHS MAP4K5 | 1.72 | PDGFRb | 2.48 | ||
| LCK | 1.88 | RAF1 | 39.66 | ||
| LOK/STK10 | 12.61 | RET | 45.99 | ||
| LRRK2 | 30.12 | RIPK2 | 25.2 | ||
| LYN | 2.13 | SIK2 | 1.91 | ||
| LYN B | 6 | SRMS | 16.98 | ||
| MEK2 | 8.43 | TEC | 11.28 | ||
| MEKK2 | 23.47 | TXK | 1.37 | ||
| MEKK3 | 11.8 | YES/YES1 | 1.94 | ||
| MELK | 25.8 | ||||
| MINK/MINK1 | 1.21 | ||||
| MLCK2/MYLK2 | 32.05 | ||||
| MLK1/MAP3K9 | 16.48 | ||||
| MLK2/MAP3K10 | 22.88 | ||||
| MLK3/MAP3K11 | 13.47 | ||||
| MST1/STK4 | 7.4 | ||||
| MST2/STK3 | 13.86 | ||||
| MST3/STK24 | 11.02 | ||||
| MST4 | 5.9 | ||||
| MYO3b | 40.28 | ||||
| NEK1 | 15.17 | ||||
| NEK2 | 8.56 | ||||
| NEK4 | 32.6 | ||||
| PAK1 | 11.68 | ||||
| PAK3 | 9.9 | ||||
| PKCa | 49.46 | ||||
| PKCd | 40.27 | ||||
| PKCmu/PRKD1 | 43.71 | ||||
| PKCnu/PRKD3 | 42.25 | ||||
| PKD2/PRKD2 | 35.54 | ||||
| PYK2 | 32.56 | ||||
| RET | 18.94 | ||||
| RSK3 | 44.2 | ||||
| SIK2 | 1.93 | ||||
| SLK/STK2 | 21.59 | ||||
| STK25/YSK1 | 10.1 | ||||
| SYK | 21.1 | ||||
| TAK1 | 28.29 | ||||
| TRKC | 15.25 | ||||
| TXK | 27.53 | ||||
| TYRO3 SKY | 47.75 | ||||
| WEE1 | 40.47 | ||||
| YES/YES1 | 7.29 | ||||
| Bos-I | Dasatinib | ||||
| Kinase inhibited% of overlap | 84 | 35 | |||
| 41.7 | |||||
| Remaining Kinase activity (%) | |||||
| Kinases inhibited by: | Bos-I | Dasatinib | Inhibitor potency (Dasatinib / Bos-I) | ||
| ABL1 | 1.8 | 2.77 | 1.5 | ||
| ABL2/ARG | 2.19 | 2.74 | 1.3 | ||
| ACK1 | 3.54 | 2.62 | 0.7 | ||
| ARK5/NUAK1 | 11.43 | 15.93 | 1.4 | ||
| BLK | 20.73 | 3.04 | 0.1 | ||
| BMX/ETK | 14.48 | 2.53 | 0.2 | ||
| BTK | 5.69 | 2.09 | 0.4 | ||
| CSK | 12.33 | 7.11 | 0.6 | ||
| c-SRC | 6.05 | 3.52 | 0.6 | ||
| EGFR | 3.84 | 21.08 | 5.5 | ||
| EPHA2 | 9.58 | 6.82 | 0.7 | ||
| EPHA3 | 31.66 | 3.46 | 0.1 | ||
| EPHA4 | 27.01 | 1.63 | 0.1 | ||
| EPHA5 | 37.14 | 0.24 | 0.0 | ||
| EPHA8 | 10.52 | 4.13 | 0.4 | ||
| EPHB1 | 11.8 | 4.8 | 0.4 | ||
| EPHB2 | 17.43 | 0 | 0.0 | ||
| EPHB3 | 49.42 | 0.99 | 0.0 | ||
| EPHB4 | 12.48 | 1.17 | 0.1 | ||
| ERBB4/HER4 | 1.53 | 4.03 | 2.6 | ||
| FGR | 11.49 | 1.7 | 0.1 | ||
| FMS | 43.09 | 0.77 | 0.0 | ||
| FRK/PTK5 | 29.2 | 0 | 0.0 | ||
| FYN | 29.42 | 1.96 | 0.1 | ||
| HCK | 11.88 | 0.79 | 0.1 | ||
| HGK MAP4K4 | 1.03 | 49.2 | 47.8 | ||
| KHS MAP4K5 | 1.72 | 3.07 | 1.8 | ||
| LCK | 1.88 | 0.31 | 0.2 | ||
| LYN | 2.13 | 0.43 | 0.2 | ||
| LYN B | 6 | 1.6 | 0.3 | ||
| MINK/MINK1 | 1.21 | 46.54 | 38.5 | ||
| RET | 18.94 | 45.99 | 2.4 | ||
| SIK2 | 1.93 | 1.91 | 1.0 | ||
| TXK | 27.53 | 1.37 | 0.0 | ||
| YES/YES1 | 7.29 | 1.94 | 0.3 | ||
The % residual activity is shown. A comparison of inhibitor potency of dasatinib / Bos-I is shown (right) and values shown in red denote kinases inhibited more potently (>2-fold) inhibited by Bos-I compared with dasatinib.