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Encorafenib (LGX818) BRAF inhibitor

Name: Encorafenib (LGX818)
Brand: Selleck Chemicals
SKU: S7108
Availability: InStock
Rating: 5 (38 reviews)

Cat.No.S7108

Encorafenib (LGX818) is a highly potent RAF inhibitor with selective anti-proliferative and apoptotic activity in cells expressing B-RAF(V600E) with EC50 of 4 nM. This compound has reached Phase 3.

Chemical Structure

Molecular Weight: 540.01

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.81%

99.81

Related Targets	Ras ERK p38 MAPK JNK MEK S6 Kinase MAP4K TAK1 Mixed Lineage Kinase ASK MNK MAPKAPK2 KLF TOPK
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Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
A375	Function assay	2 days	Inhibition of B-Raf V600E mutant in human A375 cells harboring B-Raf V600E mutant assessed as reduction in cell proliferation incubated for 2 days by Bright-Glo luminescence assay, IC50 = 0.002 μM.	ChEMBL
A549	Function assay	30 mins	Inhibition of IL1-beta-induced p38alpha phosphorylation in human A549 cells pre-incubated for 30 mins before IL1-beta stimulation and measured after 7 to 8 hrs post IL1-beta stimulation by Bright-Glo luciferase reporter gene assay, IC50 = 2.2 μM.	ChEMBL
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	540.01	Formula	C₂₂ H₂₇ Cl F N₇ O₄ S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1269440-17-6	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	LGX818			Smiles	CC(C)N1C=C(C(=N1)C2=C(C(=CC(=C2)Cl)NS(=O)(=O)C)F)C3=NC(=NC=C3)NCC(C)NC(=O)OC

Solubility

In vitro
Batch:

DMSO : 100 mg/mL ( (185.18 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 7 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
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.
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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (9.26mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
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.
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.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Features	Orally bioavailable RAF-selective inhibitor.
Targets/IC₅₀/Ki	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. ^[1]
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. ^[1]
References	http://cancerres.aacrjournals.org/content/72/8_supplement/3790 https://pubmed.ncbi.nlm.nih.gov/28611198/

Applications

Methods	Biomarkers	Images	PMID
Western blot	p-ERK / ERK / p-MEK / MEK / p-p90RSK / p90RSK BIM / Mcl-1 / Bcl2 / Bcl-xl / NOXA / MITF / c-myc / PARP / Cleaved caspase Cyclin D1 / CDC6 / CDK2 p21CIP1 / p27KIP1 / pRb p-mTOR / pp70S6K		29210065
Growth inhibition assay	Cell viability		26586345

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT02834364	Completed	Relapsed or Refractory Multiple Myeloma\|Patients With BRAFV600 E or BRAFV600K Mutation	University of Heidelberg Medical Center\|Array BioPharma\|German Cancer Research Center\|Coordinating Centre for Clinical Trials Heidelberg\|University Hospital Heidelberg	June 2016	Phase 2
NCT02278133	Completed	Metastatic Colorectal Cancer	Array BioPharma	December 2014	Phase 1\|Phase 2
NCT01909453	Active not recruiting	Melanoma	Pfizer	September 16 2013	Phase 3
NCT01719380	Completed	Colorectal Cancer	Pfizer	November 23 2012	Phase 2
NCT01436656	Completed	Melanoma and Metastatic Colorectal Cancer	Pfizer	September 5 2011	Phase 1

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