Asciminib (ABL001) selectively inhibited the growth of CML and Ph+ ALL cells with potencies ranging from 1-10nM range. Asciminib was tested for activity against clinically observed mutations and found to be active in the low nM range. In the KCL-22 mouse xenograft model, Asciminib displayed potent anti-tumor activity with complete tumor regression observed and a clear dose-dependent correlation with pSTAT5 inhibition. The oral bioavailability of ABL001 in mouse and rat are 35% and 27% respectively when dosed at 30 mg/kg p.o. While in dogs the oral BA of ABL001 is 111% (15 mg/kg, p.o).
| Molecular Weight | 449.84 |
| Formula | C20H18ClF2N5O3 |
| CAS Number | 1492952-76-7 |
| Solubility (25°C) | DMSO 90 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[1] Wylie AA, et al. Nature. The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1.
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