Encorafenib (LGX818)

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.

Encorafenib (LGX818) Chemical Structure

CAS No. 1269440-17-6

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

Purity & Quality Control

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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=>
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)

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
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)

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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.
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Molarity Calculator

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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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