In vitro: HA15 induces ER stress leading to cancer cell death in vitro and overcomes BRAF inhibitor resistance in melanoma cells. In vivo: HA15 induces ER stress leading to cancer cell death and exhibits strong efficacy in xenograft mouse models with melanoma cells either sensitive or resistant to BRAF inhibitors.
| Cell Experiment | |
|---|---|
| Cell lines | A375 cells |
| Preparation method | Electron microscopic images of A375 cells treated for 24 hr with HA15 displayed membrane blebs characteristic of apoptotic cells。 |
| Concentrations | 10 μM |
| Incubation time | 24 h |
| Animal Experiment | |
|---|---|
| Animal models | female athymic nude mice |
| Formulation | |
| Dosages | 0.7 mg/mouse/day |
| Administration | i.v. |
| Molecular Weight | 466.58 |
| Formula | C23H22N4O3S2 |
| CAS Number | 1609402-14-3 |
| Solubility (25°C) | 73 mg/mL in DMSO |
| 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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