Forchlorfenuron (FCF) is a synthetic cytokinin that inhibits septins and exhibits anti-parasitic, anticancer, and anti-angiogenic activities. Forchlorfenuron is also a plant growth regulator. Cytotoxicity of forchlorfenuron and its metabolites are tested through Sulforhodamine B assays against CHO cells. Forchlorfenuron exhibits significant cytotoxicity against CHO cells with an IC50 of 12.12±2.14 μM.
In live mammalian cells, FCF dampens septin dynamics and induces the assembly of abnormally large septin structures. FCF has a low level of cytotoxicity, and these effects are reversed upon FCF washout. Significantly, FCF treatment induces mitotic and cell migration defects that phenocopy the effects of septin depletion by small interfering RNA. FCF targets the filamentous assembly of divergent septin isoforms (e.g. Cdc3/10/11/12 (42), SEPT2, SEPT7) reversibly and across species.
Forchlorfenuron (FCF) has low oral toxicity in rats with an LD50 of 4940 mg/kg bw in male rats and 4899 mg/kg bw in females.
| Cell Experiment | |
|---|---|
| Cell lines | HeLa or MDCK cells |
| Preparation method | HeLa or MDCK cells are plated overnight on collagen-coated 35-mm tissue culture dishes and then treated with DMSO or FCF for 4 h. Cells are trypsinized, resuspended in DMEM supplemented with 10% FBS, and mixed in a 1:1 ratio with trypan blue at room temperature for 1 min. Blue and non-blue cells are counted using a hemocytometer. |
| Concentrations | 6.25-500 μM |
| Incubation time | 4 h |
| Animal Experiment | |
|---|---|
| Animal models | toxicity test of forchlorfenuron in rats |
| Formulation | - |
| Dosages | 4940 mg/kg bw in male rats and 4899 mg/kg bw in females |
| Administration | oral |
| Molecular Weight | 247.68 |
| Formula | C12H10ClN3O |
| CAS Number | 68157-60-8 |
| Form | Solid |
| Solubility (25°C) | DMSO: 30 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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