PTC596 is a novel BMI-1 inhibitor, downregulating MCL-1 and inducing p53-independent mitochondrial apoptosis in acute myeloid leukemia progenitor cells. PTC596 inhibits myeloid leukemia cell growth in vivo while sparing normal hematopoietic cells.
| Cell Experiment | |
|---|---|
| Cell lines | Z-138 and REC-1 cells |
| Preparation method | Z-138 and REC-1 cells were treated for 24 hours with 300 nM PTC596, after which BCL-2, BCL-XL and MCL-1 protein levels were determined. |
| Concentrations | 300 nM |
| Incubation time | 24 h |
| Animal Experiment | |
|---|---|
| Animal models | Non-obese diabetic-severe combined immunodeficiency (NOD-SCID)/IL2Rγ-KO (NSG) mice |
| Formulation | 0.5% hydroxypropyl methylcellulose and 0.1% Tween 80 in distilled water |
| Dosages | 5 mg/kg |
| Administration | oral gavage |
| Molecular Weight | 420.34 |
| Formula | C19H13F5N6 |
| CAS Number | 1610964-64-1 |
| Form | Solid |
| Solubility (25°C) | DMSO 60 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.
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