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RK-33 is a first-in-class, potent and selective DDX3 (RNA helicase) inhibitor, it binds to DDX3 and abrogates its activity. RK-33 caused G1 cell cycle arrest, induced apoptosis, and promoted radiation sensitization in DDX3-overexpressing cells. Inhibition of DDX3 by RK-33 also promotes tumor regression, thus providing a compelling argument to develop DDX3 inhibitors for lung cancer therapy. RK-33 radiosensitizes prostate cancer cells by blocking the RNA helicase DDX3.
| Cell Experiment | |
|---|---|
| Cell lines | MDA-MB-231 cells |
| Preparation method | Healthy, 60-70% confluent MDA-MB-231 cells are transduced with shDDX3 lentivirus particles. Knockdown of DDX3 expression is confirmed both by qRT-PCR and immunoblotting. MDA-MB-231 cells are treated with RK-33 (7.5 μM) for 12 h and harvested for RNA. Microarray experiments are performed. |
| Concentrations | 7.5 μM |
| Incubation time | 12 h |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | |
| Dosages | |
| Administration | |
| 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.
| Molecular Weight | 428.44 |
| Formula | C23H20N6O3 |
| CAS Number | 1070773-09-9 |
| Purity | >99% |
| Solubility | DMSO 30 mg/mL |
| Storage | at -20°C |
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