Molecular Formula | C22H27ClFN7O4S |
Molar Mass | 540.01 |
Density | 1.45±0.1 g/cm3(Predicted) |
Melting Point | 184-185°C |
Solubility | DMSO (Slightly), Methanol (Slightly) |
Appearance | Solid |
Color | White to Off-White |
pKa | 5.94±0.10(Predicted) |
Storage Condition | -20°C Freezer, Under inert atmosphere |
In vitro study | LGX818 treated A375 (BRAFV600E) human melanoma cell line, inhibited phospho-ERK (EC50=3 nM), effectively inhibited proliferation (EC50=4 nM). LGX818 had no significant activity on a panel of 100 kinases (IC50>900 nM), and LGX818 did not inhibit the 400 of multiple cell lines expressing wild-type BRAF. In biochemical experiments, the dissociation Half-Life> 24 hours translates into sustained target inhibition followed by washout of the drug. |
In vivo study | In a single-dose PK/PD study, LGX818 was administered orally at a low dose of 6 mg/kg to a human melanoma xenograft model (BRAFV600E), which was potent (75%) and durable (over 24 hours). Reduce phospho-MEK. LGX818 was treated at a low dose of 1 mg/kg in immunocompromised mice and rats and induced tumor regression in a variety of human xenograft models with BRAF mutations. Consistent with the in vitro data, LGX818 was inactive against BRAF wild-type tumors with good tolerability and linear growth even at doses up to 300 mg/kg twice daily. LGX818 was also effective in more disease-related models of spontaneous metastatic melanoma and melanoma brain metastases. LGX818 is a potent and selective RAF kinase inhibitor with unique biochemical properties. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 1.852 ml | 9.259 ml | 18.518 ml |
5 mM | 0.37 ml | 1.852 ml | 3.704 ml |
10 mM | 0.185 ml | 0.926 ml | 1.852 ml |
5 mM | 0.037 ml | 0.185 ml | 0.37 ml |