Home MAPK Raf inhibitor - MEK inhibitor Avutometinib For research use only.

Avutometinib

Synonyms: RO5126766,CH5126766,VS 6766, CKI-27, R-7304, RG-7304

Avutometinib(RO5126766,CH5126766,VS 6766, CKI-27, R-7304, RG-7304) is a dual RAF/MEK inhibitor with IC50 of 8.2 nM,19 nM, 56 nM, and 160 nM for BRAF V600E, BRAF, CRAF, and MEK1, respectively. Phase 1.

Avutometinib Chemical Structure

Avutometinib Chemical Structure

CAS: 946128-88-7

Selleck's Avutometinib has been cited by 16 publications

Purity & Quality Control

Batch: Purity: 99.54%
99.54

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Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HCT116 cell Function assay 96 h Inhibition of human HCT116 cell growth after 96 hrs by counting kit-8 analysis, IC50=0.04 μM 24900832
human C32 cells Growth inhibition assay Growth inhibition of human C32 cells harboring R-Raf V600E mutant, IC50=0.047 μM 24900832
human PANC1 cells Function assay 10 μM 1 h Inhibition of MEK1 in human PANC1 cells assessed as reduction in pErk1/2 level at 10 uM after 1 hr by Western blotting analysis 25766633
human A549 cells Function assay 10 μM 1 h Inhibition of MEK1 in human A549 cells assessed as reduction in pErk1/2 level at 10 uM after 1 hr by Western blotting analysis 25766633
Click to View More Cell Line Experimental Data

Biological Activity

Description Avutometinib(RO5126766,CH5126766,VS 6766, CKI-27, R-7304, RG-7304) is a dual RAF/MEK inhibitor with IC50 of 8.2 nM,19 nM, 56 nM, and 160 nM for BRAF V600E, BRAF, CRAF, and MEK1, respectively. Phase 1.
Targets
BRAF V600E [1]
(cell-free assay)		 BRAF [1]
(cell-free assay)		 CRAF [1]
(cell-free assay)		 MEK1 [1]
(cell-free assay)
8.2 nM 19 nM 56 nM 160 nM
In vitro
In vitro

In HCT116 KRAS-mutant colorectal cancer cells, CH5126766 significantly reduces the levels of phospho-MEK and phospho-ERK. CH5126766 inhibits RAF kinase by binding to MEK1, and causes MEK to become a dominant negative inhibitor of RAF. [1] In Raf or RAS-mutant cell lines SK-MEL-28, SK-MEL-2, MIAPaCa-2, SW480, HCT116, and PC3 cells, CH5126766 inhibits cell growth with IC50 of 65, 28, 40, 46, and 277 nM, respectively. In two melanoma cell lines with the BRAF V600E or NRAS mutation, RO5126766 induces G1 cell cycle arrest accompanied by up-regulation of the CDK inhibitor p27 and down-regulation of cyclinD1. [3]
Kinase Assay MEK and RAF kinase enzyme assays
The inhibitory activities against CRAF, BRAF, or BRAF V600E enzymes are measured by quantification of phosphorylation of inactive K97R MEK1 [MEK1] by recombinant RAF proteins [BRAF: B-RAF wt, BRAF V600E: B-RAF V600E or CRAF: Raf-1] with Europium-anti-MEK1/2 (pSer218/222) antibody and SureLight allophycocyanine-anti-6his antibody by measuring time-resolved fluorescence (TRF). Alternatively, the inhibitory activities against the RAF enzymes are measured by quantification of phosphorylation of a fluorescein-labeled peptide corresponding to human MEK1 212-224 and human MEK2 217-229 (5-Fl-SGQLIDSMANSFV-NH2, MEKtide) by using the IMAP fluorescence polarization (FP) Screening Express Kit. Inhibition of MEK1 is evaluated by a coupled assay with active MEK1 (MEK1 S218E/S222E) and unactive dephosphorylated ERK2 (MAP kinase 2/Erk 2). The phosphorylation of a fluorescent-labeled peptide substrate (FAM-Erktide, IPTTPITTTYFFFK-5FAM-COOH) by ERK2 is quantified by using the IMAP FP Screening Express Kit.
Cell Research Cell lines SK-MEL-28, SK-MEL-2, MIAPaCa-2, SW480, A549, HCT15, HCT116, and PC3 cells
Concentrations ~10 μM
Incubation Time 72 h
Method

The number of viable cells is determined using the Cell Counting Kit-8 assay according to the manufacturer's instructions. After the incubation of cells for 72 h with the indicated concentrations of various agents, kit reagent WST-8 is added to the medium and incubated for a further 4 h. The absorbance of samples (450 nm) is determined using a scanning multiwell spectrophotometer that serves as an ELISA reader. Cell numbers and viability are also measured using the ViaCount Assay according to the manufacturer's instructions.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-MEKR / MEK / p-ERK / ERK / p27 / ppRB / pRB / Cyclin D1 / Cyclin E 25422890
In Vivo
In vivo

In an HCT116 (G13D KRAS) mouse xenograft model, CH5126766 (25 mg/kg, p.o.) inhibits ERK signaling output more effectively than a standard MEK inhibitor that induces MEK phosphorylation and has potent antitumor activity. [1] In the HCT116 (K-ras) and COLO205 (B-raf) mutant xenografts, CH5126766 (0.3 mg/kg) causes significant decreases in [18 F]FDG uptake. [2] In the SK-MEL-2 xenograft model, RO5126766 also suppresses the tumor growth. [3]
Animal Research Animal Models Female BALB-nu/nu mice bearing HCT116, Calu-6 or COLO205 tumors
Dosages ~25 mg/kg
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06104488 Recruiting Refractory Cancer|CNS Tumors|CNS Tumor Adult|CNS Tumor Childhood|MAP Kinase Family Gene Mutation|NF1|Plexiform Neurofibroma|Low-grade Glioma|Optic Pathway Gliomas|Neuroblastoma|Primary Brain Tumor|Solid Tumor|Solid Tumor Adult|Solid Carcinoma|Central Nervous System Tumor Memorial Sloan Kettering Cancer Center October 20 2023 Phase 1
NCT05375994 Recruiting Non Small Cell Lung Cancer|KRAS Activating Mutation|Advanced Cancer|Metastatic Cancer|Malignant Neoplasm of Lung|Malignant Neoplastic Disease Verastem Inc.|Mirati Therapeutics Inc. August 1 2022 Phase 1|Phase 2
NCT05074810 Recruiting Non Small Cell Lung Cancer|KRAS Activating Mutation Verastem Inc.|Amgen April 12 2022 Phase 1|Phase 2

Chemical lnformation & Solubility

Molecular Weight 471.46 Formula

C21H18FN5O5S
CAS No. 946128-88-7 SDF Download Avutometinib SDF
Smiles CC1=C(C(=O)OC2=C1C=CC(=C2)OC3=NC=CC=N3)CC4=C(C(=NC=C4)NS(=O)(=O)NC)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 94 mg/mL ( (199.38 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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