LY3009120
LY3009120 is a pan-RAF and RAF dimer inhibitor. It inhibits BRAF WT, CRAF, WT, BRAFV600E, and BRAFV600E+G468A with the IC50 values of 9.1, 15, 5.8, and 17 nM, respectively. [1]
RAF is family of serine/threonine-protein kinase mediates Ras GTPases and the MAPK/ERK cascade. It involves in proliferation, differentiation, apoptosis, survival and oncogenic transformation. [1]
In NRAS mutant SK-Mel2 cells or KRAS mutant HCT116 cells, LY3009120 inhibits the kinase activity of CRAF in a dose-dependent manner and induces BRAF/CRAF heterodimerization. It also blocks Phospho-MEK and -ERK and induces minimal paradoxical activation in RAS mutant Cells. Moreover, treatment of BRAF V600E A375 melanoma cells by LY3009120 for 24 hr predominantly induces a G0/G1 arrest with more than 95% cells in G0/G1 phase. [1]
In nude rats bearing A375 xenograft tumors, oral LY3001920 treatment exerts a dose-dependent inhibition of phospho-MEK and –ERK. 15 or 30 mg/kg LY3009120 shows near complete tumor regression in nude rats bearing PDX tumors. [1]
Reference:
1. Peng SB, Henry JR, Kaufman MD et al. Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers. Cancer Cell. 2015 Sep 14;28(3):384-98.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 424.51 |
| Cas No. | 1454682-72-4 |
| Formula | C23H29FN6O |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥4.25 mg/mL in DMSO with gentle warming and ultrasonic |
| Chemical Name | 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)pyrido[2,3-d]pyrimidin-3-yl)phenyl)urea |
| SDF | Download SDF |
| Canonical SMILES | CC1=NC2=NC(NC)=NC=C2C=C1C3=CC(NC(NCCC(C)(C)C)=O)=C(F)C=C3C |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
A375 cells and HCT116 cells |
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Preparation method |
This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.5 μM, 24, 72 h |
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Applications |
LY3009120 suppresses the proliferation of melanoma cells with either BRAF or NRAS mutation. It also induces cell cycle G0/G1 arrest and apoptosis in tumor cells with RAS or BRAF mutation. |
| Animal experiment [1]: | |
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Animal models |
Female NIH nude rats bearing xenograft tumors |
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Dosage form |
Oral administration, 5, 10, or 15 mg/kg, twice daily |
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Application |
Treatment of rat bearing melanoma BRAF V600E A375 xenograft tumors by 5, 10, or 15 mg/kg, twice daily of LY3009120, induced tumor growth inhibition and regression in a dose-dependent manner. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Peng S B, Henry J R, Kaufman M D, et al. Inhibition of RAF isoforms and active dimers by LY3009120 leads to anti-tumor activities in RAS or BRAF mutant cancers[J]. Cancer Cell, 2015, 28(3): 384-398. | |
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