Home MAPK Raf inhibitor Encorafenib For research use only.

Encorafenib

Synonyms: LGX818

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.

Encorafenib Chemical Structure

Encorafenib Chemical Structure

CAS: 1269440-17-6

Selleck's Encorafenib has been cited by 27 Publications

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Purity & Quality Control

Batch: Purity: 99.81%
99.81

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Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation 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
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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.
Features Orally bioavailable RAF-selective inhibitor.
Targets
B-Raf (V600E) [1]
In vitro
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 Research Cell lines A375 cells
Concentrations 40 nM
Incubation Time 24 h
Method

Different concentrations of encorafenib were incubated with cells for 24 h.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-mTOR / pp70S6K p21CIP1 / p27KIP1 / pRb Cyclin D1 / CDC6 / CDK2 BIM / Mcl-1 / Bcl2 / Bcl-xl / NOXA / MITF / c-myc / PARP / Cleaved caspase p-ERK / ERK / p-MEK / MEK / p-p90RSK / p90RSK 26586345
Growth inhibition assay Cell viability 26586345
In Vivo
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]
Animal Research Animal Models Female nude mice bearing A375 (BRAF V600E) human melanoma tumor xenografts
Dosages 5 mg/kg
Administration Oral
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 December 13 2013 Phase 3
NCT01719380 Completed Colorectal Cancer Pfizer November 23 2012 Phase 2
NCT01543698 Completed Solid Tumors Harboring a BRAF V600 Mutation Pfizer May 28 2012 Phase 1|Phase 2

Chemical lnformation & Solubility

Molecular Weight 540.01 Formula

C22 H27 Cl F N7 O4 S
CAS No. 1269440-17-6 SDF --
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
Storage (From the date of receipt)

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


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In vivo
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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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