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L-779450 suppressed DNA synthesis and induced apoptosis in hematopoietic FDC-P1 cells transformed to grow in response to either Raf-1 or A-Raf (FD/DeltaRaf-1:ER and FD/DeltaA-Raf:ER), but it displayed less effects on DNA synthesis and apoptosis when the cells were cultured in IL-3. L-779450 was less effective on B-Raf- or MEK1-responsive cells. Treatment with L779450, but not PLX4720, induced strong KSR1/B-Raf binding in A549 and HMCB cells that possess oncogenic Ras proteins, in the Cal12T line that contains an impaired activity B-Raf mutant, and, surprisingly, in A375 melanoma cells that are homozygous for V600E-B-Raf. L779450-induced B-Raf/C-Raf dimerization was not reduced in MEFs expressing the R615H- and C809Y-KSR1 mutants unable to bind B-Raf; whereas B-Raf/C-Raf dimerization was abolished in cells expressing S297A/S392A-KSR1 that exhibits enhanced inhibitor-induced B-Raf binding.
| Molecular Weight | 347.8 |
| Formula | C20H14ClN3O |
| CAS Number | 303727-31-3 |
| Solubility (25°C) | ≥ 34 mg/mL in DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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