SC1 is a dual function small molecule inhibitor of both ERK1 and RasGAP and that simultaneous inhibition of both protein activities is required and sufficient for SC1’s effects on mES cells. SC1 activates Ras by inhibition of RasGAP function. SC1 improved the derivation efficiency and pluripotency of ES cells from C57BL/6. Three types of pluripotent stem cells (fES, ntES, and iPS cells) of the C57BL/6 background could generate full-term pups with high efficiency when cultured with SC1.
Cell Experiment | |
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Cell lines | Mouse ES cells |
Preparation method | mES cells are seeded in gelatin-coated six-well plates at 1.6×104 cells/cm2 and maintained with 3 μM SC1 in ESC-SR media, 1 μM SC1 in ESC-N2B27 media, or 300 nM SC1 in ESC-N2 media without LIF or feeder cells. mES cells maintained with 103 units/ml LIF plus 10 ng/ml BMP4 in ESC-N2B27 media are used as a positive control. mES cells treated with DMSO in ESC-SR media, ESC-N2B27 media, or ESC-N2 media for two passages are used as negative controls. Cells are split every 3 days and seeded at same density (1.6×104 cells/cm2). mES cells at passage 11 are analyzed with FACS, immunocytochemistry, histocytochemistry, and RT-PCR. |
Concentrations | 300 nM, 1 μM, 3 μM |
Incubation time |
Animal Experiment | |
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Animal models | |
Formulation | |
Dosages | |
Administration |
Molecular Weight | 550.53 |
Formula | C27H25F3N8O2 |
CAS Number | 839707-37-8 |
Solubility (25°C) | 100 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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