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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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Purity: ≥98%
Encorafenib (formerly LGX818; LGX-818; trade name Braftovi), an approved anticancer drug, is a highly potent, and orally bioavailable B-RAFV600E inhibitor with potential antineoplastic activity. With an IC50 of 4 nM, it inhibits B-Raf V600E. Against BRAF of the wild type, it has little impact. Encorafenib was given FDA approval in June 2018 to treat metastatic or irresectable melanoma. On cells expressing BRAFV600E, encorafenib has selective anti-proliferative and apoptotic activity. With more than 400 cell lines expressing BRAFV600E, it exhibits no discernible activity against a panel of 100 kinases and no inhibition of cell growth. Encorafenib oral administration results in a significant decrease in phospho-MEK and causes tumor regression in human melanoma xenograft models. In the RAFMAPK/ERK signaling pathway, Raf kinase is a serine/threonine enzyme. Encorafenib may lessen the proliferation of tumor cells by preventing the activation of the RAF/MAPK/ERK signaling pathway.
| Targets |
B-Raf (V600E) (IC50 = 0.3 nM)
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| ln Vitro |
Encorafenib (LGX818) is a potent medication that can prevent illnesses or conditions linked to abnormal or uncontrolled kinase activity, especially illnesses or conditions involving abnormal activation of B-Raf[1]. In A375, G361 and SK-MEL-24 cells, encorafenib (LGX818) (10 nM) significantly inhibits pERK and suppresses the ERK/MAPK pathway. A375, G361 and SK-MEL-24 cells are potently inhibited from forming colonies when exposed to 10 nM Encorafenib (LGX818) for 12 days, but RPMI7951 and C8161 cells are not. In G361 cells, encorafenib (LGX818) treatment causes a progressive rise in the concentration of β-catenin[2].
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| ln Vivo |
Encorafenib treatment at oral doses as low as 6 mg/kg resulted in a 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). In multiple BRAF mutant human tumor xenograft models grown in immunocompromised mice and rats, LGX818 induces tumor regression at doses as low as 1 mg/kg. According to in vitro data, LGX818 is ineffective against BRAF wild-type tumors at doses up to 300 mg/kg bid, with good tolerability and linear exposure increase. Additionally, effectiveness is attained in a model of brain metastasizing melanoma as well as a spontaneous metastatic melanoma that is more disease-relevant. LGX818 is a potent and selective RAF kinase inhibitor with unique biochemical properties that contribute to an excellent pharmacological profile. [1]
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| Enzyme Assay |
The addition of 10 L of 2×ATP diluted in assay buffer per well initiates the Raf kinase activity reaction. The reactions are terminated after 3 hours (bRaf(V600E)) or 1 hour (c-Raf) by adding 10 μL of stop reagent (60 mM EDTA). By adding 30 μL of a mixture of the antibody (1:2000 dilution) and detection beads (1:2000 dilution of both beads) in bead buffer (50 mM Tris, pH 7.5, 0.01% Tween20) to the well, phosphorylated product is measured using a rabbit anti-p-MEK antibody and the Alpha Screen IgG (ProteinA) detection Kit. To prevent light from damaging the detection beads, the additions are performed in a dark environment. A PerkinElmer Envision instrument is used to read the luminescence after an hour of room temperature incubation with a lid on top of the plate. Using XL Fit data analysis software, non-linear regression is used to determine the concentration of each compound that results in 50% inhibition (IC50).
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| Cell Assay |
Cells were incubated with encorafenib at various concentrations for 24 hours.
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| Animal Protocol |
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| References |
| Molecular Formula |
C22H27CLFN7O4S
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| Molecular Weight |
540.01
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| Exact Mass |
539.15
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| Elemental Analysis |
C, 48.93; H, 5.04; Cl, 6.57; F, 3.52; N, 18.16; O, 11.85; S, 5.94
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| CAS # |
1269440-17-6
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| Related CAS # |
Encorafenib-13C,d3
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| Appearance |
Solid powder
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| SMILES |
C[C@@H](CNC1=NC=CC(=N1)C2=CN(N=C2C3=C(C(=CC(=C3)Cl)NS(=O)(=O)C)F)C(C)C)NC(=O)OC
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| InChi Key |
CMJCXYNUCSMDBY-ZDUSSCGKSA-N
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| InChi Code |
InChI=1S/C22H27ClFN7O4S/c1-12(2)31-11-16(17-6-7-25-21(28-17)26-10-13(3)27-22(32)35-4)20(29-31)15-8-14(23)9-18(19(15)24)30-36(5,33)34/h6-9,11-13,30H,10H2,1-5H3,(H,27,32)(H,25,26,28)/t13-/m0/s1
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| Chemical Name |
methyl N-[(2S)-1-[[4-[3-[5-chloro-2-fluoro-3-(methanesulfonamido)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.63 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.63 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2.5 mg/mL (4.63 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (4.63 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 6: 5%DMSO+40%PEG300+5%Tween80+50%ddH2O: 100mg/ml Solubility in Formulation 7: 16.67 mg/mL (30.87 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8518 mL | 9.2591 mL | 18.5182 mL | |
| 5 mM | 0.3704 mL | 1.8518 mL | 3.7036 mL | |
| 10 mM | 0.1852 mL | 0.9259 mL | 1.8518 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04655157 | Active Recruiting |
Drug: encorafenib Drug: nivolumab |
Melanoma | Jason J. Luke, MD | May 28, 2021 | Phase 1 Phase 2 |
| NCT05004350 | Active Recruiting |
Drug: Encorafenib Drug: Cetuximab |
BRAF V600E Metastatic Colorectal Cancer |
Pierre Fabre Medicament | September 14, 2021 | Phase 2 |
| NCT01909453 | Active Recruiting |
Drug: LGX818 Drug: MEK162 |
Melanoma | Pfizer | December 13, 2013 | Phase 3 |
| NCT03973918 | Active Recruiting |
Drug: Encorafenib Drug: Binimetinib |
BRAF V600E BRAF V600K |
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
July 29, 2019 | Phase 2 |
| NCT03543969 | Active Recruiting |
Drug: Encorafenib Drug: Binimetinib |
Melanoma (Skin) Skin Cancer |
H. Lee Moffitt Cancer Center and Research Institute |
June 14, 2018 | Early Phase 1 |
Fig. 1. LGX818 suppresses the ERK/MAPK pathway, inhibits proliferation and induces cell cycle arrest in BRAFV600E melanoma cells.Cancer Lett.2016 Jan 28;370(2):332-44. |
Fig. 2.LGX818 downregulates CyclinD1 dependent of DYRK1B, but not GSK3β.Cancer Lett.2016 Jan 28;370(2):332-44. |
Fig. 3. Apoptosis is not involved in LGX818-mediated melanoma cell growth inhibition.Cancer Lett.2016 Jan 28;370(2):332-44. |
Fig. 4. LGX818 induces senescence in BRAFV600E melanoma cells.Cancer Lett.2016 Jan 28;370(2):332-44. |
Fig. 5. LGX818 enhances autophagic flux and induces autophagy via inhibition of the mTOR pathway in BRAFV600E melanoma cells.Cancer Lett.2016 Jan 28;370(2):332-44. |
Fig. 6. Autophagy is involved in LGX818-induced senescence in BRAFV600E melanoma cells.Cancer Lett.2016 Jan 28;370(2):332-44. |
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