product name Encorafenib
Description: Encorafenib, also known as LGX818, is a highly potent B-RAF(V600E) inhibitor with EC50 of 4 nM. It has little effect against wild-type BRAF. Encorafenib has selective anti-proliferative and apoptotic activity ion in cells expressing BRAFV600E. It shows no significant activity against a panel of 100 kinases and no suppression of cell growth with more than 400 cell lines expressing BRAFV600E. In the A375 human melanoma cell line. In human melanoma xenograft models, oral administration of Encorafenib shows strong decrease in phospho-MEK and induces tumor regression.
References: [1] Cancer Res, 2012, 72(8 Supplement): 3790; [2] J Hematol Oncol. 2013 Apr 25;6:30
540.01
Formula
C22H27ClFN7O4S
CAS No.
1269440-17-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (185.2 mM)
Water: <1 mg/mL
Ethanol: 100 mg/mL (185.2 mM)
Solubility (In vivo)
Synonyms
LGX818
other peoduct :
| In Vitro |
In vitro activity: In the A375 (BRAFV600E) human melanoma cell line LGX818 suppresses phospho-ERK (EC50 = 3 nM) leading to potent inhibition of proliferation (EC50 = 4 nM). No significant activity is observed against a panel of 100 kinases (IC50 > 900 nM) and LGX818 does not inhibit proliferation of > 400 cell lines expressing wild-type BRAF. Contributing to the high potency of LGX818 is the extremely slow off-rate from BRAFV600E which is not observed with other RAF inhibitors. In biochemical assays the dissociation half-life is >24 hours which translated into sustained target inhibition in cells following drug wash-out. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | LGX818 treatment at oral doses as low as 6 mg/kg resulted in strong (75%) and sustained (>24 hours) decrease in phospho-MEK, even following clearance of drug from circulation in single dose PK/PD studies in human melanoma xenograft models (BRAFV600E). LGX818 induces tumor regression in multiple BRAF mutant human tumor xenograft models grown in immune compromised mice and rats at doses as low as 1 mg/kg. Consistent with the in vitro data, LGX818 is inactive against BRAF wild-type tumors at doses up to 300 mg/kg bid, with good tolerability and linear increase in exposure. Efficacy is also achieved in a more disease-relevant spontaneous metastatic melanoma and a model of melanoma brain metastasis. LGX818 is a potent and selective RAF kinase inhibitor with unique biochemical properties that contribute to an excellent pharmacological profile. |
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| Formulation & Dosage | |
| References | [1] Darrin D Stuart, et al. Cancer Res, 2012, 72(8 Supplement): 3790; [2] J Hematol Oncol. 2013 Apr 25;6:30 |
