SBI-0640756 is a first-in-class inhibitor that targets eIF4G1 and disrupts the eIF4F complex. SBI-0640756 impaired the eIF4F complex assembly independently of mTOR and attenuated growth of BRAF-resistant and BRAF-independent melanomas. SBI-0640756 (SBI-756) inhibits the growth of NRAS, BRAF, and NF1-mutant melanomas in vitro.
In vivo, SBI-0640756 (SBI-756) delays the onset and reduces the incidence of Nras/Ink4a melanomas.
| Cell Experiment | |
|---|---|
| Cell lines | Melanoma lines |
| Preparation method | Melanoma lines are plated (triplicates 384-well plates; 1,500 cells per well) and cell viability is assessed 48 hours after treatment with indicated compounds. Growth inhibition is calculated as percentage of DMSO-treated controls and is plotted against the log drug concentration. |
| Concentrations | 1, 2, 5 μmol/L |
| Incubation time | 48 h |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | |
| Dosages | |
| Administration | |
| Molecular Weight | 404.82 |
| Formula | C23H14ClFN2O2 |
| CAS Number | 1821280-29-8 |
| 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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