LGX818 (Encorafenib)

Catalog No.S7108 Batch:S710803

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Technical Data

Formula

C22 H27 Cl F N7 O4 S
Molecular Weight 540.01 CAS No. 1269440-17-6
Solubility (25°C)* In vitro DMSO 100 mg/mL (185.18 mM)
Ethanol 6 mg/mL (11.11 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Encorafenib is a highly potent RAF inhibitor with selective anti-proliferative and apoptotic activity in cells expressing B-RAF(V600E) with EC50 of 4 nM. Phase 3.
Targets
B-Raf (V600E) [1]
In vitro

In the A375 (BRAFV600E) human melanoma cell line, Encorafenib (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 it does not inhibit proliferation of > 400 cell lines expressing wild-type BRAF. Contributing to the high potency of this compound 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.

In vivo

Encorafenib (LGX818) is a potent and selective RAF kinase inhibitor with unique biochemical properties that contribute to an excellent pharmacological profile. Treatment with this compound 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). It 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, it 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.

Features Orally bioavailable RAF-selective inhibitor.

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    A375 cells

  • Concentrations

    40 nM

  • Incubation Time

    24 h

  • Method

    Encorafenib (LGX818) was incubated with cells at different concentrations for 24 h.
Animal Study:

[2]
  • Animal Models

    Female nude mice bearing A375 (BRAF V600E) human melanoma tumor xenografts

  • Dosages

    5 mg/kg

  • Administration

    Oral

References

  • http://cancerres.aacrjournals.org/content/72/8_supplement/3790
  • https://pubmed.ncbi.nlm.nih.gov/28611198/

Customer Product Validation

<p>Whole cell lysates from NRAS- or BRAF-mutant melanoma cells treated with encorafenib or/and binimetinib or DMSO as a control for 24 h were subjected to Western blot analysis to detect pERK, ERK and β-Actin. Experiment shown is a representative of three independent experiments.</p>

, , Clin Cancer Res, 2017, 23(20):6203-6214

<p>(E) A375 and G361 cells were transfected with GFP-mRFP-LC3 for 24 h, then they were treated the same as in (D) for 4 and 24 h. Images were taken with a confocal microscope.</p>

, , Cancer Lett, 2016, 370(2):332-44.

Selleck's LGX818 (Encorafenib) Has Been Cited by 43 Publications

Off-targets of BRAF inhibitors disrupt endothelial signaling and vascular barrier function [ Life Science Alliance, June 05, 2024, e202402671] PubMed: 38839106
Methotrexate sensitizes drug-resistant metastatic melanoma cells to BRAF V600E inhibitors dabrafenib and encorafenib [ Oncotarget, January 29, 2018, 13324-13336] PubMed: 29568360
Second-generation BRAF inhibitor Encorafenib resistance is regulated by NCOA4-mediated iron trafficking in the drug-resistant malignant melanoma cells [ Scientific Reports, January 18, 2025, 2422] PubMed: 39827294
BRAFV600 and ErbB inhibitors directly activate GCN2 in an off-target manner to limit cancer cell proliferation [ bioRxiv, December 20, 2024, nan]
Combined inhibition of focal adhesion kinase and RAF/MEK elicits synergistic inhibition of melanoma growth and reduces metastases [ Cell Rep Med, 2025, 6(2):101943] PubMed: 39922199
HDAC and MEK inhibition synergistically suppresses HOXC6 and enhances PD-1 blockade efficacy in BRAFV600E-mutant microsatellite stable colorectal cancer [ J Immunother Cancer, 2025, 13(1)e010460] PubMed: 39800382
Novel CDK2/CDK9 inhibitor fadraciclib targets cell survival and DNA damage pathways and synergizes with encorafenib in human colorectal cancer cells with BRAF(V600E) [ Oncogenesis, 2025, 14(1):27] PubMed: 40769976
Strong Hsp90α/β Protein Expression in Advanced Primary CRC Indicates Short Survival and Predicts Response to the Hsp90α/β-Specific Inhibitor Pimitespib [ Cells, 2025, 14(11)836] PubMed: 40498011
Second-generation BRAF inhibitor Encorafenib resistance is regulated by NCOA4-mediated iron trafficking in the drug-resistant malignant melanoma cells [ Sci Rep, 2025, 15(1):2422] PubMed: 39827294
Adaptive Plasticity Tumor Cells Modulate MAPK-Targeting Therapy Response in Colorectal Cancer [ bioRxiv, 2025, 2025.01.22.634215] PubMed: 39896605

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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