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Encorafenib (LGX818)

Name: Encorafenib (LGX818)
Brand: Selleck Chemicals
SKU: S7108
Rating: 5 (17 reviews)

Catalog No.S7108

For research use only.

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. Phase 3.

CAS No. 1269440-17-6

Selleck's Encorafenib (LGX818) has been cited by 17 publications

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Raf Signaling Pathway Map

Biological Activity

Description

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. Phase 3.

Features

Orally bioavailable RAF-selective inhibitor.

Targets

B-Raf (V600E) ^[1]
()

In vitro

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. ^[1]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

A375	MVPGeY5kfGmxbjDhd5NigQ>?		MVqyJIRigXN?		NYXBTGdSUW6qaXLpeIlwdiCxZjDCMXJi\iCYNkCwSUBufXSjboSgbY4hcHWvYX6gRVM4PSClZXzsd{Bp[XKkb4LpcochSi2UYX[gWlYxOEVibYX0ZY51KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBk\WyuIIDyc4xq\mW{YYTpc44hcW6ldXLheIVlKG[xcjCyJIRigXNiYomgRpJq\2i2LVfsc{BtfW2rbnXzZ4Vv[2ViYYPzZZktKEmFNUCgQUAxNjByMjFOwG0v	NV3pd5lJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzNyMU[xNk8oRkOqRV3CUFww[T5?
A549	MVjGeY5kfGmxbjDhd5NigQ>?		MofLN\|AhdWmwcx?=		MknBTY5pcWKrdHnvckBw\iCLTEGtZoV1[S2rbnT1Z4VlKHB\|OHHsdIhiKHCqb4PwbI9zgWyjdHnvckBqdiCqdX3hckBCPTR7IHPlcIx{KHC{ZT3pcoN2[mG2ZXSg[o9zKDNyIH3pcpMh[mWob4LlJGlNOS2kZYThJJN1cW23bHH0bY9vKGGwZDDt[YF{fXKnZDDh[pRmeiB5IITvJFghcHK\|IIDvd5QhUUxzLXLleIEhe3SrbYXsZZRqd25iYomgRpJq\2i2LVfsc{BtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZZN{[XluIFnDOVAhRSB{LkKg{txONg>?	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzN\|AyPjF{Lze+R4hGVUKOPD;hQi=>

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	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 26586345
Growth inhibition assay	Cell viability	26586345

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. ^[1]

Protocol (from reference)

References

[1] Darrin D Stuart, et al. Cancer Res, 2012, 72(8 Supplement): 3790

Solubility (25°C)

In vitro	DMSO	100 mg/mL (185.18 mM)
	Ethanol	100 mg/mL (185.18 mM)
	Water	Insoluble

Chemical Information

Molecular Weight	540.01
Formula	C₂₂ H₂₇ Cl F N₇ O₄ S
CAS No.	1269440-17-6
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
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

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.

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT02834364	Active not recruiting	Drug: Encorafenib\|Drug: Binimetinib	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	Drug: WNT974\|Drug: LGX818\|Biological: Cetuximab	Metastatic Colorectal Cancer	Array BioPharma	December 2014	Phase 1\|Phase 2
NCT01909453	Active not recruiting	Drug: LGX818\|Drug: MEK162\|Drug: vemurafenib	Melanoma	Pfizer	December 13 2013	Phase 3
NCT01719380	Completed	Drug: LGX818\|Drug: Cetuximab\|Drug: BYL719	Colorectal Cancer	Pfizer	November 23 2012	Phase 2
NCT01543698	Active not recruiting	Drug: LGX818\|Drug: MEK162\|Drug: LEE011	Solid Tumors Harboring a BRAF V600 Mutation	Pfizer	May 30 2012	Phase 1\|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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